Paired-housing selectively facilitates within-session extinction of avoidance behavior, and increases c-Fos expression in the medial prefrontal cortex, in anxiety vulnerable Wistar-Kyoto rats.

PubMed

Smith, Ian M; Pang, Kevin C H; Servatius, Richard J; Jiao, Xilu; Beck, Kevin D

2016-10-01

The perseveration of avoidance behavior, even in the absence of once threatening stimuli, is a key feature of anxiety and related psychiatric conditions. This phenomenon can be observed in the Wistar-Kyoto (WKY) rat which, in comparison to outbred controls, demonstrates impaired extinction of avoidance behavior. Also characteristic of the WKY rat is abnormalities of the neurocircuitry and neuroplasticity of the medial prefrontal cortex (mPFC). One means of reducing physiological responses to anxiety, and conditioned fear, in social species is the presence of a conspecific animal. The current study investigates whether or not pair-housed WKY rats would show facilitated extinction of avoidance in comparison to individual-housed WKY rats, and whether or not pair-housing influences mPFC activation during lever-press avoidance. Male WKY rats were assigned to individual-housed and pair-housed conditions. Rats were trained in lever-press avoidance. Each session of lever-press avoidance consisted of 20 trials, where pressing a lever in response to a warning tone prevented foot-shocks. Rats received 12 acquisition sessions over 4weeks; followed by 6 extinction sessions over 2weeks, where foot-shocks ceased to be delivered. Brains were harvested 90min after trials 1 and 10 of extinction sessions 1 and 6, and mPFC sections underwent c-Fos staining as a measure of activation. Pair-housed rats showed facilitated lever-press avoidance extinction rates, but the main cause for this overall difference was a selective facilitation of within-session extinction. Similar to individual-housed rats, pair-housed rats continued to avoid during trial 1 of extinction even when the avoidance responding had been significantly reduced by the end of the previous session. Pair-housed rats sacrificed on trial 1 showed greater c-Fos expression in the anterior cingulate cortex and prelimbic cortex subregions of the mPFC compared individual-housed rats sacrificed on trial 1. This data shows pair

Oxytocin differently regulates pressor responses to stress in WKY and SHR rats: the role of central oxytocin and V1a receptors.

PubMed

Wsol, A; Szczepanska-Sadowska, E; Kowalewski, S; Puchalska, L; Cudnoch-Jedrzejewska, A

2014-01-01

The role of central oxytocin in the regulation of cardiovascular parameters under resting conditions and during acute stress was investigated in male normotensive Wistar-Kyoto (WKY; n = 40) and spontaneously hypertensive rats (SHR; n = 28). In Experiment 1, mean arterial blood pressure (MABP) and heart rate (HR) were recorded in WKY and SHR rats at rest and after an air-jet stressor during intracerebroventricular (ICV) infusions of vehicle, oxytocin or oxytocin receptor (OTR) antagonist. In Experiment 2, the effects of vehicle, oxytocin and OTR antagonist were determined in WKY rats after prior administration of a V1a vasopressin receptor (V1aR) antagonist. Resting MABP and HR were not affected by any of the ICV infusions either in WKY or in SHR rats. In control experiments (vehicle), the pressor response to stress was significantly higher in SHR. Oxytocin enhanced the pressor response to stress in the WKY rats but reduced it in SHR. During V1aR blockade, oxytocin infusion entirely abolished the pressor response to stress in WKY rats. Combined blockade of V1aR and OTR elicited a significantly greater MABP response to stress than infusion of V1a antagonist and vehicle. This study reveals significant differences in the regulation of blood pressure in WKY and SHR rats during alarming stress. Specifically, the augmentation of the pressor response to stress by exogenous oxytocin in WKY rats is caused by its interaction with V1aR, and endogenous oxytocin regulates the magnitude of the pressor response to stress in WKY rats by simultaneous interaction with OTR and V1aR.

Effect of γ-aminobutyric acid and nattokinase-enriched fermented beans on the blood pressure of spontaneously hypertensive and normotensive Wistar-Kyoto rats.

PubMed

Suwanmanon, Kanintra; Hsieh, Pao-Chuan

2014-12-01

In this study we have evaluated the changes in arterial blood pressure in spontaneously hypertensive rats (SHR) caused by the short-term intake of Bacillus subtilis B060-fermented beans with significant γ-aminobutyric acid (GABA) and nattokinase activity. After being weaned, 7-week-old male SHR and 7-week-old male Wistar-Kyoto (WKY) rats were randomized into seven groups. Until the 8 th week of life, the rats in each group were given one of the following: Group 1, high dose of GABA and nattokinase in the SHR (SHD); Group 2, medium dose of GABA and nattokinase in the SHR (SMD); Group 3, low dose of GABA and nattokinase in the SHR (SLD); Group 4, negative control in the SHR (SD); Group 5, positive control in the SHR (SM); Group 6, high dose of GABA and nattokinase in the WKY (WHD); and Group 7, negative control in the WKY (WD). Distilled water served as the negative control, and captopril (50 mg/kg), a known ACE inhibitor, served as the positive control. Systolic blood pressure and diastolic blood pressure values were measured weekly from the 8 th week to the 16 th week of life using the tail-cuff method. A definite decrease in systolic and diastolic blood pressure values could be observed in the rats treated with captopril and in the rats that received GABA and nattokinase. The greatest antihypertensive effect was observed when the pharmacological treatment was administered. The effect of the daily intake of fermented beans containing GABA and nattokinase may be helpful in controlling blood pressure levels in hypertensive model animals. The fermentation of beans with B. subtilis B060 may therefore constitute a successful strategy for producing a functional food with antihypertensive activity. Copyright © 2014. Published by Elsevier B.V.

Transient Receptor Potential Channel Opening Releases Endogenous Acetylcholine, which Contributes to Endothelium-Dependent Relaxation Induced by Mild Hypothermia in Spontaneously Hypertensive Rat but Not Wistar-Kyoto Rat Arteries.

PubMed

Zou, Q; Leung, S W S; Vanhoutte, P M

2015-08-01

Mild hypothermia causes endothelium-dependent relaxations, which are reduced by the muscarinic receptor antagonist atropine. The present study investigated whether endothelial endogenous acetylcholine contributes to these relaxations. Aortic rings of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were contracted with prostaglandin F2 α and exposed to progressive mild hypothermia (from 37 to 31°C). Hypothermia induced endothelium-dependent, Nω-nitro-l-arginine methyl ester-sensitive relaxations, which were reduced by atropine, but not by mecamylamine, in SHR but not in WKY rat aortae. The responses in SHR aortae were also reduced by acetylcholinesterase (the enzyme responsible for acetylcholine degradation), bromoacetylcholine (inhibitor of acetylcholine synthesis), hemicholinium-3 (inhibitor of choline uptake), and vesamicol (inhibitor of acetylcholine release). The mild hypothermia-induced relaxations in both SHR and WKY rat aortae were inhibited by AMTB [N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)-benzamide; the transient receptor potential (TRP) M8 inhibitor]; only those in SHR aortae were inhibited by HC-067047 [2-methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide; TRPV4 antagonist] while those in WKY rat aortae were reduced by HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; TRPA1 antagonist]. The endothelial uptake of extracellular choline and release of cyclic guanosine monophosphate was enhanced by mild hypothermia and inhibited by HC-067047 in SHR but not in WKY rat aortae. Compared with WKY rats, the SHR preparations expressed similar levels of acetylcholinesterase and choline acetyltransferase, but a lesser amount of vesicular acetylcholine transporter, located mainly in the endothelium. Thus, mild hypothermia causes nitric oxide-dependent relaxations by opening TRPA1 channels in WKY rat aortae

Behavioral variability in SHR and WKY rats as a function of rearing environment and reinforcement contingency.

PubMed Central

Hunziker, M H; Saldana, R L; Neuringer, A

1996-01-01

The spontaneously hypertensive rat (SHR) may model aspects of human attention deficit hyperactivity disorder (ADHD). For example, just as responses by children with ADHD tend to be variable, so too SHRs often respond more variably than do Wistar-Kyoto (WKY) control rats. The present study asked whether behavioral variability in the SHR strain is influenced by rearing environment, a question related to hypotheses concerning the etiology of human ADHD. Some rats from each strain were reared in an enriched environment (housed socially), and others were reared in an impoverished environment (housed in isolation). Four groups--enriched SHR, impoverished SHR, enriched WKY, and impoverished WKY--were studied under two reinforcement contingencies, one in which reinforcement was independent of response variability and the other in which reinforcement depended upon high variability. The main finding was that rearing environment did not influence response variability (enriched and impoverished subjects responded similarly throughout). However, rearing environment affected body weight (enriched subjects weighted more than impoverished subjects) and response rate (impoverished subjects generally responded faster than enriched subjects). In addition, SHRs tended to respond variably throughout the experiment, whereas WKYs were more sensitive to the variability contingencies. Thus, behavioral variability was affected by genetic strain and by reinforcement contingency but not by the environment in which the subjects were reared. PMID:8583193

Decrease of Perivascular Adipose Tissue Browning Is Associated With Vascular Dysfunction in Spontaneous Hypertensive Rats During Aging.

PubMed

Kong, Ling-Ran; Zhou, Yan-Ping; Chen, Dong-Rui; Ruan, Cheng-Chao; Gao, Ping-Jin

2018-01-01

Functional perivascular adipose tissue (PVAT) is necessary to maintain vascular physiology through both mechanical support and endocrine or paracrine ways. PVAT shows a brown adipose tissue (BAT)-like feature and the browning level of PVAT is dependent on the anatomic location and species. However, it is not clear whether PVAT browning is involved in the vascular tone regulation in spontaneously hypertensive rats (SHRs). In the present study, we aimed to illustrate the effect of aging on PVAT browning and subsequent vasomotor reaction in SHRs. Herein we utilized histological staining and western blot to detect the characteristics of thoracic PVAT (tPVAT) in 8-week-old and 16-week-old SHR and Wistar-Kyoto (WKY) rats. We also detected vascular reactivity analysis to determine the effect of tPVAT on vasomotor reaction during aging. The results showed that tPVAT had a similar phenotype to BAT, including smaller adipocyte size and positive uncoupling protein-1 (UCP1) staining. Interestingly, the tPVAT of 8-week-old SHR showed increased BAT phenotypic marker expression compared to WKY, whereas the browning level of tPVAT had a more dramatic decrease from 8 to 16 weeks of age in SHR than age-matched WKY rats. The vasodilation effect of tPVAT on aortas had no significant difference in 8-week-old WKY and SHR, whereas this effect is obviously decreased in 16-week-old SHR compared to WKY. In contrast, tPVAT showed a similar vasoconstriction effect in 8- or 16-week-old WKY and SHR rats. Moreover, we identified an important vasodilator adenosine, which regulates adipocyte browning and may be a potential PVAT-derived relaxing factor. Adenosine is dramatically decreased from 8 to 16 weeks of age in the tPVAT of SHR. In summary, aging is associated with a decrease of tPVAT browning and adenosine production in SHR rats. These may result in attenuated vasodilation effect of the tPVAT in SHR during aging.

Differential cardiotoxicity in response to chronic doxorubicin treatment in male spontaneous hypertension-heart failure (SHHF), spontaneously hypertensive (SHR), and Wistar Kyoto (WKY) rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharkey, Leslie C., E-mail: shark009@umn.edu; Radin, M. Judith, E-mail: radin.1@osu.edu; Heller, Lois, E-mail: lheller@d.umn.edu

Life threatening complications from chemotherapy occur frequently in cancer survivors, however little is known about genetic risk factors. We treated male normotensive rats (WKY) and strains with hypertension (SHR) and hypertension with cardiomyopathy (SHHF) with 8 weekly doses of doxorubicin (DOX) followed by 12 weeks of observation to test the hypothesis that genetic cardiovascular disease would worsen delayed cardiotoxicity. Compared with WKY, SHR demonstrated weight loss, decreased systolic blood pressure, increased kidney weights, greater cardiac and renal histopathologic lesions and greater mortality. SHHF showed growth restriction, increased kidney weights and renal histopathology but no effect on systolic blood pressure ormore » mortality. SHHF had less severe cardiac lesions than SHR. We evaluated cardiac soluble epoxide hydrolase (sEH) content and arachidonic acid metabolites after acute DOX exposure as potential mediators of genetic risk. Before DOX, SHHF and SHR had significantly greater cardiac sEH and decreased epoxyeicosatrienoic acid (EET) (4 of 4 isomers in SHHF and 2 of 4 isomers in SHR) than WKY. After DOX, sEH was unchanged in all strains, but SHHF and SHR rats increased EETs to a level similar to WKY. Leukotriene D4 increased after treatment in SHR. Genetic predisposition to heart failure superimposed on genetic hypertension failed to generate greater toxicity compared with hypertension alone. The relative resistance of DOX-treated SHHF males to the cardiotoxic effects of DOX in the delayed phase despite progression of genetic disease was unexpected and a key finding. Strain differences in arachidonic acid metabolism may contribute to variation in response to DOX toxicity. - Highlights: • Late doxorubicin toxicity evaluated in normal, hypertensive, and cardiomyopathic rats. • Hypertension enhances the delayed toxicity of doxorubicin. • Genetic predisposition to cardiomyopathy did not further enhance toxicity. • Epoxyeicosatrienoic

Atrial Arrhythmia in Ageing Spontaneously Hypertensive Rats: Unraveling the Substrate in Hypertension and Ageing

PubMed Central

Lau, Dennis H.; Shipp, Nicholas J.; Kelly, Darren J.; Thanigaimani, Shivshankar; Neo, Melissa; Kuklik, Pawel; Lim, Han S.; Zhang, Yuan; Drury, Karen; Wong, Christopher X.; Chia, Nicholas H.; Brooks, Anthony G.; Dimitri, Hany; Saint, David A.; Brown, Lindsay; Sanders, Prashanthan

2013-01-01

Background Both ageing and hypertension are known risk factors for atrial fibrillation (AF) although the pathophysiological contribution or interaction of the individual factors remains poorly understood. Here we aim to delineate the arrhythmogenic atrial substrate in mature spontaneously hypertensive rats (SHR). Methods SHR were studied at 12 and 15 months of age (n = 8 per group) together with equal numbers of age-matched normotensive Wistar-Kyoto control rats (WKY). Electrophysiologic study was performed on superfused isolated right and left atrial preparations using a custom built high-density multiple-electrode array to determine effective refractory periods (ERP), atrial conduction and atrial arrhythmia inducibility. Tissue specimens were harvested for structural analysis. Results Compared to WKY controls, the SHR demonstrated: Higher systolic blood pressure (p<0.0001), bi-atrial enlargement (p<0.05), bi-ventricular hypertrophy (p<0.05), lower atrial ERP (p = 0.008), increased atrial conduction heterogeneity (p = 0.001) and increased atrial interstitial fibrosis (p = 0.006) & CD68-positive macrophages infiltration (p<0.0001). These changes resulted in higher atrial arrhythmia inducibility (p = 0.01) and longer induced AF episodes (p = 0.02) in 15-month old SHR. Ageing contributed to incremental bi-atrial hypertrophy (p<0.01) and atrial conduction heterogeneity (p<0.01) without affecting atrial ERP, fibrosis and arrhythmia inducibility. The limited effect of ageing on the atrial substrate may be secondary to the reduction in CD68-positive macrophages. Conclusions Significant atrial electrical and structural remodeling is evident in the ageing spontaneously hypertensive rat atria. Concomitant hypertension appears to play a greater pathophysiological role than ageing despite their compounding effect on the atrial substrate. Inflammation is pathophysiologically linked to the pro-fibrotic changes in the hypertensive atria. PMID:24013508

Neophobia in spontaneous hypertensive (SHR) and normotensive control (WKY) rats.

PubMed

Delini-Stula, A; Hunn, C

1985-03-01

Latency of approaching a novel object (white-colored cube) placed in an unfamiliar open field, duration of object exploration, ambulation, rearing, grooming, and defecation were investigated in spontaneous hypertensive rats (SHR), their genetic normotensive controls (WKY), and standard Laboratory rats of Wistar origin (Tif:RAIf). The parameters measured were taken as indices of fear due to novelty (neophobia). Remarkable differences in behavior of all three strains were observed. By comparison to RAIf and WKY rats, SHR showed decreased neophobia as reflected in the significantly shorter latency of approaching the object and enhanced ambulation and rearing activity in the open field. By comparison to RAIf rats SHR also showed reduced grooming and defecation. WKY rats distinguished themselves from both SHR and RAIf by almost total absence of all responses in this test situation. This behavioral suppression was antagonized by 7.5 mg/kg ip of chlordiazepoxide. The results of this study further support the notion that, by comparison to standard laboratory rats, both SHR and WKY rats show possible genetically determined, altered behaviors which are diametrically opposite to each other.

CONSISTENT INFLAMMATORY RESPONSE FOLLOWING EXPOSURE TO CONCENTRATED AMBIENT PARTICLES (CAPS) DURING FALL SEASON IN WISTAR-KYOTO RATS

EPA Science Inventory

CONSISTENT INFLAMMATORY RESPONSE FOLLOWING EXPOSURE TO CONCENTRATED AMBIENT PARTICLES (CAPs) DURING FALL SEASON IN WISTAR-KYOTO RATS.
UP Kodavanti, MC Schladweiler, AD Ledbetter, LC Walsh, PS Gilmour, MI Gilmour, WP Watkinson, JP Nolan, JH Richards, D Andrews, DL Costa. US EPA...

Dietary intake of rapeseed oil as the sole fat nutrient in Wistar rats--lack of increase in plasma lipids and renal lesions.

PubMed

Ohara, Naoki; Naito, Yukiko; Nagata, Tomoko; Tachibana, Shigehiro; Okimoto, Mari; Okuyama, Harumi

2008-12-01

Dietary rapeseed (canola) oil (CO) given as the only fat nutrient shortens life in stroke-prone spontaneously hypertensive rats (SHRSP), compared with SHRSP given soybean oil (SO) instead of CO. CO ingestion increases plasma lipids and causes renal lesions in SHRSP and in spontaneously hypertensive rats (SHR), and increases plasma lipids also in Wistar Kyoto (WKY) rats, a normotensive counterpart of SHR. This study examined whether or not such unfavorable effects of CO are restricted to these closely related strains. For this purpose Wistar rats, the strain from which these strains were derived, were fed a diet containing 10% CO or SO as the sole fat nutrient for 10 weeks, and changes in clinical signs, urinalysis, blood biochemistry and pathology were compared. CO ingestion did not induce any abnormalities in Wistar rats, except significant increases in plasma concentrations of aldosterone and Na(+), compared with the SO group. Thus, the unfavorable effects of CO ingestion appear to be restricted to SHRSP and its closely related strains. The role of increased aldosterone and Na(+ )in the unfavorable events caused by CO in SHRSP, SHR and WKY rats, and any factors which could induce such increases in aldosterone and Na(+), remain to be elucidated.

The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats

PubMed Central

Chen, Lu-jing; Shen, Bing-qing; Liu, Dan-dan; Li, Sheng-tian

2014-01-01

Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood. PMID:24839560

Increased Ca2+ sensitivity of contractile elements via protein kinase C in alpha-toxin permeabilized SMA from young spontaneously hypertensive rats.

PubMed

Sasajima, H; Shima, H; Toyoda, Y; Kimura, K; Yoshikawa, A; Hano, T; Nishio, I

1997-10-01

The purpose of the present investigation was to examine the Ca2+ sensitivity of the contractile elements via protein kinase C (PKC) in superior mesenteric artery (SMA) from young (5-6 weeks old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Staphylococcal aureus alpha-toxin, which produces pores in the plasma membrane too small to allow passage of proteins such as PKC, was used to investigate the signal transduction system in vascular smooth muscle cells. We investigated the Ca2+ sensitivity of the contractile apparatus via PKC in intact and alpha-toxin skinned SMA from young SHR and WKY. In intact SMA, high K+ responses were not different between SHR and WKY. However, phorbol 12,13-dibutyrate (PDBu, a PKC activator) augmented high K(+)-evoked contractions and PKC inhibitors, such as 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) and calphostin C, suppressed them more in SHR as compared with WKY. In alpha-toxin skinned SMA, the [Ca2+]i-force relationship curve was not significantly different between SHR and WKY. However, PDBu augmented [Ca2+]i-evoked contractions and PKC inhibitors suppressed them more in SHR than in WKY. These results suggest that the Ca2+ sensitivity of the contractile elements via PKC is significantly greater in prehypertensive SHR than in age-matched WKY. This abnormality in small muscular arteries may be involved in the pathogenesis of hypertension in SHR.

Effects of dopamine agents on a schedule-induced polydipsia procedure in the spontaneously hypertensive rat and in Wistar control rats.

PubMed

Íbias, Javier; Miguéns, Miguel; Pellón, Ricardo

2016-09-01

The spontaneously hypertensive rat (SHR) has been proposed as an animal model for attention deficit hyperactivity disorder (ADHD), and typically develops excessive patterns of response under most behavioural protocols. Schedule-induced polydipsia (SIP) is the excessive water consumption that occurs as a schedule effect when food is intermittently delivered and animals are partially food- but not water-deprived. SIP has been used as a model of excessive behaviour, and considerable evidence has involved the dopaminergic system in its development and maintenance. The aim of this study was to evaluate the effects of the most common psychostimulants used in ADHD treatment on SIP, comparing their effects in SHRs with rats from control populations. SHR, Wistar Kyoto (WKY) and Wistar rats were submitted to a multiple fixed time (FT) food schedule with two components: 30 s and 90 s. The acute effects of different dopaminergic compounds were evaluated after 40 sessions of SIP acquisition. All animals showed higher adjunctive drinking under FT 30 s than FT 90 s, and SHRs displayed higher asymptotic SIP levels in FT 90 s compared to WKY and Wistar rats. SHRs were less sensitive to dopaminergic agents than control rats in terms of affecting rates of adjunctive drinking. These differences point to an altered dopaminergic system in the SHR and provide new insights into the neurobiological basis of ADHD pharmacological treatments. © The Author(s) 2016.

Augmentation of ferulic acid-induced vasorelaxation with aging and its structure importance in thoracic aorta of spontaneously hypertensive rats.

PubMed

Fukuda, Toshihiko; Kuroda, Takahiro; Kono, Miki; Hyoguchi, Mai; Tanaka, Mitsuru; Matsui, Toshiro

2015-10-01

Aging deteriorates vascular functions such as vascular reactivity and stiffness. Thus far, various reports suggest that bioactive compounds can improve vascular functions. However, few age-related studies of natural bioactive compounds are available. The present study attempted to evaluate age-related vasorelaxation of bioactive cinnamic acids, caffeic acid, and ferulic acid using aged rat thoracic aorta. Vasorelaxation was evaluated in thoracic aorta from both 8, 18, and 40 weeks old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) respectively. The result indicated that caffeic acid possessed the vasorelaxation regardless of aging in WKY and SHR. Moreover, the vasorelaxation of ferulic acid enhanced with aging in SHR. The vasorelaxation behavior was acted in an endothelium-independent manner. To access structure importance of enhanced vasorelaxation, analogues of ferulic acid were tested. In 40 weeks old SHR, 3,4-dimethoxycinnamic acid and coniferyl alcohol exhibited equivalent vasorelaxation activity with ferulic acid, providing the structural importance of methoxy-modified 3-position on the phenyl ring and 2-propenoic moiety. These results firstly demonstrated that enhanced vasorelaxation of ferulic acid with aging and 3,4-dimethoxycinnamic acid and coniferyl alcohol, along with ferulic acid, might exhibit the therapeutic potential of vasoactive power with aging.

Stressed lungs: unveiling the role of circulating stress hormones in ozone-induced lung injury and inflammation

EPA Science Inventory

Our recent work demonstrated that circulating stress hormones, epinephrine and corticosterone/cortisol, are involved in mediating ozone pulmonary effects through the activation of hypothalamus-pituitary-adrenal (HPA) axis. Adrenalectomy in Wistar Kyoto (WKY) rats diminished circu...

Differential Stiffening between the Abdominal and Thoracic Aorta: Effect of Salt Loading in Stroke-Prone Hypertensive Rats.

PubMed

Lindesay, George; Bézie, Yvonnick; Ragonnet, Christophe; Duchatelle, Véronique; Dharmasena, Chandima; Villeneuve, Nicole; Vayssettes-Courchay, Christine

2018-06-08

Central artery stiffening is recognized as a cardiovascular risk. The effects of hypertension and aging have been shown in human and animal models but the effect of salt is still controversial. We studied the effect of a high-salt diet on aortic stiffness in salt-sensitive spontaneously hypersensitive stroke-prone rats (SHRSP). Distensibility, distension, and β-stiffness were measured at thoracic and abdominal aortic sites in the same rats, using echotracking recording of the aortic diameter coupled with blood pressure (BP), in SHRSP-salt (5% salted diet, 5 weeks), SHRSP, and normotensive Wistar-Kyoto (WKY) rats. Hemodynamic parameters were measured at BP matched to that of WKY. Histological staining and immunohistochemistry were used for structural analysis. Hemodynamic isobaric parameters in SHRSP did not differ from WKY and only those from the abdominal aorta of SHRSP-salt presented decreased distensibility and increased stiffness compared with WKY and SHRSP. The abdominal and thoracic aortas presented similar thickening, increased fibrosis, and remodeling with no change in collagen content. SHRSP-salt presented a specific increased elastin disarray at the abdominal aorta level but a decrease in elastin content in the thoracic aorta. This study demonstrates the pro-stiffening effect of salt in addition to hypertension; it shows that only the abdominal aorta presents a specific pressure-independent stiffening, in which elastin disarray is likely a key mechanism. © 2018 S. Karger AG, Basel.

Angiotensin-(1-7) upregulates central nitric oxide synthase in spontaneously hypertensive rats.

PubMed

Cerrato, Bruno D; Frasch, Alejandra P; Nakagawa, Pablo; Longo-Carbajosa, Nadia; Peña, Clara; Höcht, Cristian; Gironacci, Mariela M

2012-05-09

Increased blood pressure in hypertension is hypothesized to be caused by high sympathetic nervous system (SNS) activity. Since Ang (1-7) exerts an inhibitory neuromodulatory effect on the SNS through a NO-mediated mechanism, we tested the hypothesis that Ang (1-7) alters centrally nitric oxide synthase (NOS) activity and expression in spontaneously hypertensive rats (SHR). Since NOS activity is altered in relation to the development of hypertension in rats, we evaluated the effect of Ang-(1-7) on hypothalamic NOS activity in two different ages in SHR, corresponding to a prehypertensive phase (3-4 weeks) and a established hypertension (13-14 weeks) and compared with age-matched Wistar-Kyoto (WKY) rats. NOS activity was measured by the conversion of [³H]L-arginine to citrulline. Ang-(1-7) caused an impairment in NOS activity in prehypertensive SHR (26 ± 4% reduction), while it induced an increase in NOS activity at established hypertension (48 ± 9% increase). In contrast, Ang-(1-7) did not modify NOS activity in age-matched WKY rats. In another set of experiments, Ang-(1-7) was injected into the anterior hypothalamic area, mean arterial blood pressure (MAP) was registered and after 30, 60 and 180 min nNOS expression was evaluated by Western-blot. Ang-(1-7) decreased MAP after 10 min of injection and this effect was blocked by a NOS inhibitor. nNOS expression increased after 180 min of Ang-(1-7) intrahypothalamic injection in both WKY and SHR (WKY: 3.6-fold increase above basal; SHR: 1.85-fold increase above basal). Our results suggest that Ang-(1-7) upregulates hypothalamic NOS in a hypertensive state as a compensatory and protective mechanism to combat hypertension. Copyright © 2012 Elsevier B.V. All rights reserved.

L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.

PubMed

Brooks, Wesley W; Conrad, Chester H; Robinson, Kathleen G; Colucci, Wilson S; Bing, Oscar H L

2009-02-01

The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.

*GAS-PHASE AND PARTICULATE COMPONENTS OF DIESEL EXHAUST PRODUCE DIFFERENTIAL CARDIOPHYSIOLOGICAL IMPAIRMENTS IN HEALTHY RATS

EPA Science Inventory

We recently showed that inhalation exposure of normotensive Wistar Kyoto (WKY) rats to whole diesel exhaust (DE) elicited changes in cardiac gene expression pattern that broadly mimicked gene expression in non-exposed spontaneously hypertensive rats. We hypothesized that healthy ...

Blood Pressure Interventions Affect Acute and Four-Week Diesel Exhaust Induced Pulmonary Injury in Healthy and Hypertensive Rats

EPA Science Inventory

Rationale: We recently showed that inhalation exposure of normotensive Wistar Kyoto (WKY) rats to whole diesel exhaust (DE) elicits changes in cardiac gene expression that broadly mimics expression in spontaneously hypertensive (SH) rats without DE. We hypothesized that pharmacol...

Effects of age and hypertension on α1-adrenoceptors in the major source arteries of the rat bladder and penis.

PubMed

Yono, Makoto; Tanaka, Takanori; Tsuji, Shigeki; Irie, Shin; Sakata, Yukikuni; Otani, Masayuki; Yoshida, Masaki; Latifpour, Jamshid

2011-11-16

α(1)-Adrenoceptors regulate blood pressure, regional vascular resistance and tissue blood flow. As aging and hypertension may impact pelvic arterial blood flow resulting in bladder and penile dysfunction, we investigated effects of age and hypertension on α(1)-adrenoceptors in the major source arteries of the rat bladder and penis. Using radioligand receptor binding, real-time reverse transcription-polymerase chain reaction (RT-PCR) and fluorescent microsphere infusion techniques, we compared 3 and 22-month-old male Fischer rats, and male normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Twenty-two-month-old rats and SHRs had significantly higher total α(1)-adrenoceptor density in the internal iliac artery and lower blood flow to the bladder and penis than 3-month-old and WKY rats, respectively. RT-PCR data showed an age and hypertension related increase in the expression of α(1B)-adrenoceptor mRNA in the internal iliac, vesical and internal pudendal arteries and a switch from α(1A) predominance in 3-month-old and WKY rats to α(1B)>α(1A) in 22-month-old rats and SHRs. Our data indicate the presence of age and hypertension related alterations in vascular α(1)-adrenoceptor subtype distribution and in blood flow to the rat bladder and penis. These findings suggest that pharmacological blockade of the vascular α(1B)-adrenoceptor, which could increase pelvic blood flow, may contribute to the improvement of bladder and penile dysfunctions in animal models for aging and hypertension. Copyright © 2011 Elsevier B.V. All rights reserved.

Release of atrial natriuretic peptide from rat myocardium in vitro: effect of minoxidil-induced hypertrophy.

PubMed Central

Kinnunen, P.; Taskinen, T.; Leppäluoto, J.; Ruskoaho, H.

1990-01-01

1. Ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). To examine the role of ventricular ANP levels in the secretion of ANP into the circulation, atrial and ventricular levels of immunoreactive-ANP (IR-ANP) as well as ANP messenger RNA (mRNA), and the release of IR-ANP from isolated perfused hearts, both before and after atrialectomy, were measured simultaneously in control and minoxidil-treated Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. IR-ANP levels in the ventricles of untreated, 12 month-old SHR with severe ventricular hypertrophy were increased when compared to age-matched WKY rats. Minoxidil treatment for 8 weeks in both strains resulted in a decrease in mean arterial pressure and increases in ventricular weight to body weight ratios, plasma IR-ANP concentrations (in WKY from 133 +/- 20 to 281 +/- 34 pg ml-1, P less than 0.01; in SHR from 184 +/- 38 to 339 +/- 61 pg ml-1, P less than 0.05), and in ventricular IR-ANP contents (in WKY: 53%; in SHR: 41%). A highly significant correlation was found between ventricular IR-ANP content and ventricular weight to body weight ratio (r = 0.59, P less than 0.001, n = 26). 3. When studied in vitro, in isolated perfused heart preparations, the hypertrophied ventricular tissue after atrialectomy secreted more ANP into the perfusate than ventricles of the control hearts; ventricles contributed 28%, 22%, 18% and 15% of the total ANP release to perfusate in the minoxidil-treated SHR, control SHR, minoxidil-treated WKY and control WKY, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2141796

The urinary bladder of spontaneously hypertensive rat demonstrates bladder hypertrophy, inflammation, and fibrosis but not hyperplasia

PubMed Central

Shen, Shanwei; Xia, Chun-mei; Qiao, Li-Ya

2014-01-01

The present study aims to systemically characterize the factors that are associated with urinary bladder organ enlargement in the spontaneously hypertensive rats (SHR). Material and Methods We compared the SHR to age-matched normotensive Wistar-Kyoto (WKY) control rats in the levels of bladder pro-inflammatory factors, collagen expression (type I), and detrusor smooth muscle growth. Key Findings Our results showed that enhanced inflammatory responses and fibrosis were key factors that were closely associated with bladder wall thickening in SHR. Specifically the mRNA levels of inflammatory factors interleukin (IL)-1α, IL-6 and TNFα were significantly higher in SHR than those in WKY. The SHR also had a higher number of mast cells in the suburothelium space. Type I collagen production was also significantly higher in SHR when compared to those in control rats. However, the smooth muscle content stayed the same in SHR and WKY rats. This was shown as that the ratio of α-smooth muscle actin (SMA) to the nuclear protein histone H3 showed no difference between these two rat strains. The mRNA and protein levels of proliferating cell nuclear antigen (PCNA) also showed no change in the urinary bladder of SHR and WKY. Further study showed that the phosphorylation level of Akt in the urinary bladder was not changed in SHR when compared to WKY. In contrast, the phosphorylation level of ERK1/2 was significantly higher in SHR bladder when compared to WKY. Significance These results suggest that inflammation and fibrosis are primary factors that may lead to urinary bladder hypertrophy in SHR. PMID:25445218

Myocardial myostatin in spontaneously hypertensive rats with heart failure.

PubMed

Damatto, R L; Lima, A R R; Martinez, P F; Cezar, M D M; Okoshi, K; Okoshi, M P

2016-07-15

Myostatin has been shown to regulate skeletal and cardiac muscle growth. However, its status on long-term hypertrophied myocardium has not been addressed. The purpose of this study was to evaluate the expression of myocardial myostatin and its antagonist follistatin in spontaneously hypertensive rats (SHR) with heart failure. Eighteen-month-old SHR were evaluated to identify clinical features of heart failure such as tachypnea/labored respiration and weight loss. After heart failure was detected, rats were subjected to echocardiogram and euthanized. Age-matched normotensive Wistar-Kyoto (WKY) rats were used as controls. Myostatin and follistatin protein expression was assessed by Western blotting. Statistical analysis was performed by Student's t test. All SHR (n=8) presented right ventricular hypertrophy and five had lung congestion. SHR had left chambers hypertrophy and dilation (left atrial diameter: WKY 5.73±0.59; SHR 7.28±1.17mm; p=0.004; left ventricular (LV) diastolic diameter/body weight ratio: WKY 19.6±3.1; SHR 27.7±4.7mm/kg; p=0.001), and LV systolic dysfunction (midwall fractional shortening: WKY 34.9±3.31; SHR 24.8±3.20%; p=0.003). Myocyte diameter (WKY 23.1±1.50, SHR 25.5±1.33μm; p=0.004) and myocardial interstitial collagen fraction (WKY 4.86±0.01; SHR 8.36±0.02%; p<0.001) were increased in the SHR. Myostatin (WKY 1.00±0.16; SHR 0.77±0.23 arbitrary units; p=0.035) and follistatin (WKY 1.00±0.35; SHR 0.49±0.18 arbitrary units; p=0.002) expression was lower in SHR. Myostatin and follistatin expression negatively correlated with LV diastolic diameter-to-body weight ratio and LV systolic diameter, and positively correlated with midwall fractional shortening. Myostatin and follistatin protein expression is reduced in the long-term hypertrophied myocardium from spontaneously hypertensive rats with heart failure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.

PubMed

Sehgel, Nancy L; Sun, Zhe; Hong, Zhongkui; Hunter, William C; Hill, Michael A; Vatner, Dorothy E; Vatner, Stephen F; Meininger, Gerald A

2015-02-01

Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the vascular wall. Alternatively, we hypothesized that a significant component of increased vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of vascular smooth muscle cells, and that aging would augment the contribution from vascular smooth muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both vascular smooth muscle cell stiffness and vascular smooth muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of vascular smooth muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging. © 2014 American Heart Association, Inc.

Effect of Selenium Supplementation on Redox Status of the Aortic Wall in Young Spontaneously Hypertensive Rats

PubMed Central

Ruseva, Boryana; Atanasova, Milena; Tsvetkova, Reni; Betova, Tatyana; Mollova, Margarita; Alexandrova, Margarita; Laleva, Pavlina; Dimitrova, Aneliya

2015-01-01

Selenium (Se) is an exogenous antioxidant that performs its function via the expression of selenoproteins. The aim of this study was to explore the effect of varying Se intake on the redox status of the aortic wall in young spontaneously hypertensive rats (SHR). Sixteen male Wistar Kyoto (WKY) rats and nineteen male SHR, 16-week-old, were tested after being given diets with different Se content for eight weeks. They were divided into 4 groups: control groups of WKY NSe and SHR NSe on an adequate Se diet and groups of WKY HSe and SHR HSe that received Se supplementation. The Se nutritional status was assessed by measuring whole blood glutathione peroxidase-1 (GPx-1) activity. Serum concentration of lipid hydroperoxides and serum level of antibodies against advanced glycation end products (anti-AGEs abs) were determined. Expression of GPx-1 and endothelial nitric oxide synthase (eNOS) were examined in aortic wall. Se supplementation significantly increased GPx-1 activity of whole blood and in the aortas of WKY and SHR. Decreased lipid peroxidation level, eNOS-3 expression in the aortic wall, and serum level of anti-AGEs abs were found in SHR HSe compared with SHR NSe. In conclusion, Se supplementation improved the redox status of the aortic wall in young SHR. PMID:26473024

Comparative Analysis of Mechanical Properties of PWV, NO and Ascending Aorta between WHY Rats and SHR Rats.

PubMed

Yu, Bo; Xu, De-Jun; Sun, Huan; Yang, Kun; Luo, Min

2015-09-01

The aim of this study was to compare and analyze the tensile mechanical properties of the ascending aorta (AA) in Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs), for the purpose of providing a biomechanical basis for hypertension prevention. Pulse wave velocities (PWV) and serum nitric oxide (NO) concentrations were determined in 6-month-old WKY rats and SHRs (n = 21, n = 21, respectively). Then, 20 AAs from each group were obtained for longitudinal tensile testing. The maximum stress, maximum strain, and strain at a tensile stress of 16 Kpa were greater in WKY rats than in SHRs (p < 0.05). The aortic elastic modulus and PWV value were greater in SHRs than in WKY rats (p < 0.05 for both), while NO concentrations were lower in the SHR group than in the WKY group (p < 0.05). The AA tensile mechanical properties differed between the WKY rats and SHRs, and the tensile mechanical properties of the SHR model had changed. Ascending aorta; Hypertension; Mechanical properties; Pulse wave velocity; SHR rats; WKY rats.

Gene expression suggests spontaneously hypertensive rats may have altered metabolism and reduced hypoxic tolerance.

PubMed

Ritz, Marie-Françoise; Grond-Ginsbach, Caspar; Engelter, Stefan; Lyrer, Philippe

2012-02-01

Cerebral small vessel disease (SVD) is an important cause of stroke, cognitive decline and vascular dementia (VaD). It is associated with diffuse white matter abnormalities and small deep cerebral ischemic infarcts. The molecular mechanisms involved in the development and progression of SVD are unclear. As hypertension is a major risk factor for developing SVD, Spontaneously Hypertensive Rats (SHR) are considered an appropriate experimental model for SVD. Prior work suggested an imbalance between the number of blood microvessels and astrocytes at the level of the neurovascular unit in 2-month-old SHR, leading to neuronal hypoxia in the brain of 9-month-old animals. To identify genes and pathways involved in the development of SVD, we compared the gene expression profile in the cortex of 2 and 9-month-old of SHR with age-matched normotensive Wistar Kyoto (WKY) rats using microarray-based technology. The results revealed significant differences in expression of genes involved in energy and lipid metabolisms, mitochondrial functions, oxidative stress and ischemic responses between both groups. These results strongly suggest that SHR suffer from chronic hypoxia, and therefore are unable to tolerate ischemia-like conditions, and are more vulnerable to high-energy needs than WKY. This molecular analysis gives new insights about pathways accounting for the development of SVD.

Different relations between schedule-induced polydipsia and impulsive behaviour in the Spontaneously Hypertensive Rat and in high impulsive Wistar rats: questioning the role of impulsivity in adjunctive behaviour.

PubMed

Ibias, Javier; Pellón, Ricardo

2014-09-01

Rats belonging to three different strains (15 Wistar, 8 Spontaneously Hypertensive - SHR- and 8 Wistar Kyoto - WKY-) were used to evaluate the possible relationship between different levels of impulsivity and development of schedule-induced polydipsia (SIP). We first measured the rats' levels of impulsivity by means of delay-discounting and indifference-point procedures. Secondly, development of SIP was studied under a series of fixed time 15, 30, 60 and 120s food schedules, which were counterbalanced by means of a Latin-square design. Finally, we re-assessed the rats' levels of impulsivity by replicating the delay-discounting test. The findings showed that, starting from equivalent levels of impulsivity, development of SIP differed among the groups of rats. In comparison with the rest of the animals, the SHRs were observed to attain elevated drinking rates under SIP. On the other hand, the Wistar rats which had initial high impulsivity levels similar to those of the SHRs, displayed the lowest rates of induced drinking. Moreover, low levels of impulsivity in Wistar rats prior to SIP acquisition were reflected into high drinking rates. Relation of SIP and impulsivity is questioned by present results, which gives ground to the understanding of the behavioural mechanisms involved in adjunctive behaviour and its usefulness as an animal model of excessive behaviour. Copyright © 2014 Elsevier B.V. All rights reserved.

Changes in the composition of the thoracic aortic wall in spontaneously hypertensive rats treated with losartan or spironolactone.

PubMed

Han, Wei-Qing; Wu, Ling-Yun; Zhou, Hai-Yan; Zhang, Jia; Che, Zai-Qian; Wu, Yong-Jie; Liu, Jian-Jun; Zhu, Ding-Liang; Gao, Ping-Jin

2009-05-01

1. In the present study, we compared the elastin and collagen content of thoracic aortic medial and adventitial layers from Wistar-kyoto (WKY) and spontaneously hypertensive rats (SHR). In addition, the effects of losartan, an angiotensin II receptor antagonist, and spironolactone, a mineralocorticoid receptor antagonist, on collagen and elastin content were determined. 2. Prehypertensive (4-week-old) and hypertensive (16-week-old) SHR were randomly divided into three groups treated with either 0.9% NaCl, losartan (20 mg/kg per day) or spironolactone (200 mg/kg per day). Prehypertensive and hypertensive SHR were treated for 12 and 16 weeks, respectively. Age-matched WKY rats were not treated with NaCl, losartan or spironolactone and served as the control group. 3. The medial and adventitial layers of the thoracic aorta were composed mainly of elastin and collagen, respectively, in both SHR and WKY rats. Compared with WKY rats, SHR exhibited greater collagen and elastin content in the media, but decreased collagen and elastin content in the adventitial layer. Both medial and adventitial collagen and elastin content increased significantly with age in both strains and was greater in 32-week-old rats compared with 16-week-old rats. Spironolactone treatment decreased collagen content in the media of thoracic aortas from prehypertensive SHR, whereas losartan decreased collagen content in the media of aortas from hypertensive SHR. In contrast, neither spironolactone nor losartan had any effect on adventitial collagen content in prehypertensive and hypertensive SHR. Medial collagen and elastin were positively related to pulse pressure (PP), but there was no correlation between adventitial mass or collagen content and PP or mean arterial pressure in untreated and treated SHR and WKY rats. 4. In conclusion, the composition of the medial and adventitial layers of the thoracic aorta differs and treatment of SHR with losartan and spironolactone decreases collagen content when

Role of cortical alpha-2 adrenoceptors in alcohol withdrawal-induced depression and tricyclic antidepressants

PubMed Central

Getachew, Bruk; Hauser, Sheketha R.; Csoka, Antonei B.; Taylor, Robert E.; Tizabi, Yousef

2017-01-01

Introduction Although a role for alpha-2 adrenoceptors (alpha-2 ARs) in alcohol use disorder (AUD) and depression is suggested, very little information on a direct interaction between alcohol and these receptors is available. Methods In this study adult female Wistar and Wistar-Kyoto (WKY) rats, a putative animal model of depression, were exposed to alcohol vapor 3 h daily for 10 days (blood alcohol concentration ~150 mg%) followed by daily injection of 10 mg/kg of imipramine (IMP, a selective norepinephrine NE/serotonin reuptake inhibitor) or nomifensine (NOMI, a selective NE/dopamine reuptake inhibitor). On day 11 animals were tested for open field locomotor activity (OFLA) and forced swim test (FST) and were sacrificed 2 h later for measurement of alpha-2 ARs densities in the frontal cortex and hippocampus using [3H]RX 821002 as the specific ligand. Results Chronic alcohol treatment increased the immobility in the FST, without affecting OFLA in both Wistar and WKY rats, suggesting induction of depressive-like behavior in Wistar rats and an exacerbation of this behavior in WKY rats. Alcohol treatment also resulted in an increase in cortical but not hippocampal alpha-2 ARs densities in both Wistar and WKY rats. The behavioral effects of alcohol were completely blocked by IMP and NOMI and the neurochemical effects (increases in alpha-2 ARs) were significantly attenuated by both drugs in both strains. Conclusions The results suggest a role for cortical alpha-2 ARs in alcohol withdrawal-induced depression and that selective subtype antagonists of these receptors may be of adjunct therapeutic potential in AUD-depression co-morbidity. PMID:28414989

Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca2+-Activated K+ Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension.

PubMed

Seki, Takunori; Goto, Kenichi; Kiyohara, Kanako; Kansui, Yasuo; Murakami, Noboru; Haga, Yoshie; Ohtsubo, Toshio; Matsumura, Kiyoshi; Kitazono, Takanari

2017-01-01

Endothelium-dependent hyperpolarization (EDH)-mediated responses are impaired in hypertension, but the underlying mechanisms have not yet been determined. The activation of small- and intermediate-conductance of Ca 2+ -activated K + channels (SK Ca and IK Ca ) underpins EDH-mediated responses. It was recently reported that Ca 2+ influx through endothelial transient receptor potential vanilloid type 4 channel (TRPV4) is a prerequisite for the activation of SK Ca /IK Ca in endothelial cells in specific beds. Here, we attempted to determine whether the impairment of EDH in hypertension is attributable to the dysfunction of TRPV4 and S/IK Ca , using isolated superior mesenteric arteries of 20-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto (WKY) rats. In the WKY arteries, EDH-mediated responses were reduced by a combination of SK Ca /IK Ca blockers (apamin plus TRAM-34; 1-[(2-chlorophenyl)diphenylmethl]-1H-pyrazole) and by the blockade of TRPV4 with the selective antagonist RN-1734 or HC-067047. In the SHRSP arteries, EDH-mediated hyperpolarization and relaxation were significantly impaired when compared with WKY. GSK1016790A, a selective TRPV4 activator, evoked robust hyperpolarization and relaxation in WKY arteries. In contrast, in SHRSP arteries, the GSK1016790A-evoked hyperpolarization was small and relaxation was absent. Hyperpolarization and relaxation to cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, a selective SK Ca activator, were marginally decreased in SHRSP arteries compared with WKY arteries. The expression of endothelial TRPV4 and SK Ca protein was significantly decreased in the SHRSP mesenteric arteries compared with those of WKY, whereas function and expression of IK Ca were preserved in SHRSP arteries. These findings suggest that EDH-mediated responses are impaired in superior mesenteric arteries of SHRSP because of a reduction in both TRPV4 and SK Ca input to EDH. © 2016 American

Elevated body temperature and increased blood vessel sensitivity in spontaneously hypertensive rats.

PubMed

Price, J M; Wilmoth, F R

1990-04-01

Body temperature (BT) was significantly greater in spontaneously hypertensive rats (SHR) than in Wistar-Kyoto (WKY) rats regardless of the time of day, length of rectal probe, sex, age, or commercial vendor. Bath temperature (theta) for excised aortic rings was controlled by a thermoelectric Peltier module with an accuracy of 0.1 degree C. At peak force in individual contractions of norepinephrine (NE) dose-response experiments, theta was changed from 37 to 39 degrees C. Active and resting wall tension (Tw) were increased, and the mean effective dose (ED50) was decreased in the SHR aorta with and without endothelium. For the WKY aorta, active and resting Tw were increased, but ED50 was the same with and without endothelium. These results were supported by experiments where theta was decreased from 39 to 37 degrees C and by experiments on Sprague-Dawley rats. Potassium dose-response experiments with aorta from SHR and WKY rats show an increase in sensitivity at 39 degrees C, but active Tw is the same at 39 and 37 degrees C. When compared at the BT of each rat, the NE ED50 was lower and resting Tw was higher in the SHR aorta than in the WKY aorta, but active Tw was the same.(ABSTRACT TRUNCATED AT 250 WORDS)

Strain Differences in Self-Administration of Methylphenidate and Sucrose Pellets in a Rat Model of ADHD

PubMed Central

Marusich, Julie A.; McCuddy, W. Travis; Beckmann, Joshua S.; Gipson, Cassandra D.; Bardo, Michael T.

2011-01-01

Despite its abuse potential, methylphenidate (MPH) is widely prescribed for treatment of attention deficit hyperactivity disorder (ADHD). The purpose of the present study was to examine MPH self-administration in a rat model of ADHD. Experiment 1 examined the acquisition of MPH self-administration and assessed the MPH dose-effect curve in spontaneously hypertensive rats (SHR), an inbred rat model of ADHD, Wistar Kyotos (WKY), the progenitor strain for SHR, and Sprague-Dawleys (SD), an outbred control strain. Experiment 2 replicated Experiment 1, but replaced MPH infusions with sucrose pellets. Initial acquisition of MPH self-administration was greater in SHR and SD than WKY. With extended training using an incrementing fixed ratio schedule, however, SHR and WKY did not differ in responding for MPH using the training dose (0.3 mg/kg/infusion) or other unit doses, except that SHR showed greater responding than WKY at 0.1 mg/kg/infusion. SHR also showed greater acquisition and maintenance of sucrose-reinforced responding compared to both WKY and SD. Greater initial acquisition of MPH self-administration in SHR than WKY may not be due to a strain specific difference in sensitivity to the reinforcing effect of MPH. PMID:22015805

Y1R control of sciatic nerve blood flow in the Wistar Kyoto rat.

PubMed

Twynstra, Jasna; Medeiros, Philip J; Lacefield, James C; Jackson, Dwayne N; Shoemaker, J Kevin

2012-09-01

We hypothesized that neuropeptide Y (NPY) exerts vasoconstrictor properties in sciatic nerve blood supply by a Y1 receptor (Y1R) mechanism. Using Doppler ultrasound (40MHz), we measured blood flow velocity through a sciatic nerve supply artery during infusions of NPY and/or Y1R blockade with BIBP3226 in Wistar Kyoto rats before, and following, ganglionic blockade with Hexamethonium (Hex). Following Hex infusion, mean arterial pressure (baseline: 83±18, Hex: 57±3 mm Hg) was reduced. After 30 min, the index of conductance at the sciatic nerve (velocity/MAP expressed as % baseline) started to increase from 103±35 to 127±39% baseline in the following 30 min (p<0.05). Infusion of NPY (Y1 agonist) minimized this dilatory response (Hex baseline: 99±15, NPY: 104±11% baseline; NS). This NPY-induced attenuation was, in turn, minimized by BIBP3226 (Hex baseline: 73±12, NPY+BIBP3226: 89±14% baseline). Neither NPY nor BIBP3226 infusions without Hex affected the sciatic nerve arterial conductance. We conclude that the late dilation following Hex which is reversed by Y1R activation suggests some level of sympathetic control over sciatic nerve blood flow. Copyright © 2012 Elsevier Inc. All rights reserved.

Myocardial hypoperfusion/reperfusion tolerance with exercise training in hypertension.

PubMed

Reger, Patricia O; Barbe, Mary F; Amin, Mamta; Renna, Brian F; Hewston, Leigh Ann; MacDonnell, Scott M; Houser, Steven R; Libonati, Joseph R

2006-02-01

The purpose of this study was to examine whether exercise training, superimposed on compensated-concentric hypertrophy, could increase myocardial hypoperfusion-reperfusion (H/R) tolerance. Female Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (age: 4 mo; N = 40) were placed into a sedentary (SED) or exercise training (TRD) group (treadmill running; 25 m/min, 1 h/day, 5 days/wk for 16 wk). Four groups were studied: WKY-SED (n = 10), WKY-TRD (n = 10), SHR-SED (n = 10), and SHR-TRD (n = 10). Blood pressure and heart rate were determined, and in vitro isolated heart performance was measured with a retrogradely perfused, Langendorff isovolumic preparation. The H/R protocol consisted of a 75% reduction in coronary flow for 17 min followed by 30 min of reperfusion. Although the rate-pressure product was significantly elevated in SHR relative to WKY, training-induced bradycardia reduced the rate-pressure product in SHR-TRD (P < 0.05) without an attenuation in systolic blood pressure. Heart-to-body weight ratio was greater in both groups of SHR vs. WKY-SED (P < 0.001). Absolute and relative myocardial tolerance to H/R was greater in WKY-TRD and both groups of SHR relative to WKY-SED (P < 0.05). Endurance training superimposed on hypertension-induced compensated hypertrophy conferred no further cardioprotection to H/R. Postreperfusion 72-kDa heat shock protein abundance was enhanced in WKY-TRD and both groups of SHR relative to WKY-SED (P < 0.05) and was highly correlated with absolute left ventricular functional recovery during reperfusion (R2= 0.86, P < 0.0001). These data suggest that both compensated hypertrophy associated with short-term hypertension and endurance training individually improved H/R and that increased postreperfusion 72-kDa heat shock protein abundance was, in part, associated with the cardioprotective phenotype observed in this study.

Systemic and regional flow distribution in normotensive and spontaneously hypertensive young rats subjected to lifetime beta-adrenergic receptor blockade.

PubMed

Nishiyama, K; Nishiyama, A; Pfeffer, M A; Frohlich, E D

1978-01-01

To determine quantitatively organ blood flow distribution as the result of lifelong beta-adrenergic receptor blockade, 23 and 24 normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, respectively, were treated from conception with tap water (control; 10 WKY and 8 SHR), propranolol (0.5 mg/ml drinking water; 6 WKY and 8 SHR), or timolol (0.5 mg/ml drinking water; 7 WKY and 8 SHR) via placental circulation, mothers' milk, and drinking water. At 12 weeks of age all six groups were studied hemodynamically under ether anesthesia using an electromagnetic flowmeter and radioactive carbonized (15 micrometer) microspheres. Untreated SHR demonstrated normal cardiac output (CO) and CO distribution to all organs except for myocardium and testes, thereby confirming our previous work. With either propranolol or timolol treatment the course of development and maintenance of arterial pressure was no different than the pure-tap-water-fed WKY and SHR despite an approximate 30% reduction in CO. Further, with both beta-receptor antagonists CO distribution was significantly reduced to skeletal muscle (p less than 0.001), unchanged to the heart, and increased (p less than 0.05) to the remaining organs (including kidneys and brain) in both groups. Thus, as a result of lifelong beta-adrenergic receptor blockade, CO was reduced; and this was associated with a redistribution of blood flow so that flow to the kidney, brain, and splanchnic organs could be maintained at the expense of skeletal muslce perfusion.

Increased cardiac work provides a link between systemic hypertension and heart failure.

PubMed

Wilson, Alexander J; Wang, Vicky Y; Sands, Gregory B; Young, Alistair A; Nash, Martyn P; LeGrice, Ian J

2017-01-01

The spontaneously hypertensive rat (SHR) is an established model of human hypertensive heart disease transitioning into heart failure. The study of the progression to heart failure in these animals has been limited by the lack of longitudinal data. We used MRI to quantify left ventricular mass, volume, and cardiac work in SHRs at age 3 to 21 month and compared these indices to data from Wistar-Kyoto (WKY) controls. SHR had lower ejection fraction compared with WKY at all ages, but there was no difference in cardiac output at any age. At 21 month the SHR had significantly elevated stroke work (51 ± 3 mL.mmHg SHR vs. 24 ± 2 mL.mmHg WKY; n = 8, 4; P < 0.001) and cardiac minute work (14.2 ± 1.2 L.mmHg/min SHR vs. 6.2 ± 0.8 L.mmHg/min WKY; n = 8, 4; P < 0.001) compared to control, in addition to significantly larger left ventricular mass to body mass ratio (3.61 ± 0.15 mg/g SHR vs. 2.11 ± 0.008 mg/g WKY; n = 8, 6; P < 0.001). SHRs showed impaired systolic function, but developed hypertrophy to compensate and successfully maintained cardiac output. However, this was associated with an increase in cardiac work at age 21 month, which has previously demonstrated fibrosis and cell death. The interplay between these factors may be the mechanism for progression to failure in this animal model. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Prohedonic Effect of Cannabidiol in a Rat Model of Depression.

PubMed

Shoval, Gal; Shbiro, Liat; Hershkovitz, Liron; Hazut, Noa; Zalsman, Gil; Mechoulam, Raphael; Weller, Aron

2016-01-01

Accumulating evidence suggests that cannabidiol (CBD) may be an effective and safe anxiolytic agent and potentially also an antidepressant. The objective of this study was to further examine these properties of CBD using the 'depressive-like' Wistar-Kyoto (WKY) rat, focusing on the drug's effect on anhedonia-like behaviors. Forty-eight WKY and 48 control Wistar adult male rats were pretreated orally with CBD (15, 30 and 45 mg/kg) or vehicle. The saccharin preference test (SPT), the elevated plus maze (EPM) test and the novel object exploration (NOE) test were used. CBD showed a prohedonic effect on the WKY rats at 30 mg/kg in the SPT. In the NOE, CBD increased exploration of the novel object and locomotion at 45 mg/kg and increased locomotion at 15 mg/kg, indicating an improvement in the characteristically low motivation of WKY rats to explore. There was no similar effect at any dose in the EPM or in open-field behavior in the habituation to the NOE. These findings extend the limited knowledge on the antidepressant effect of CBD, now shown for the first time in a genetic animal model of depression. These results suggest that CBD may be beneficial for the treatment of clinical depression and other states with prominent anhedonia. © 2016 S. Karger AG, Basel.

Different reactivity to angiotensin II of peripheral and renal arteries in spontaneously hypertensive rats: effect of acute and chronic angiotensin converting enzyme inhibition

NASA Technical Reports Server (NTRS)

Guidi, E.; Hollenberg, N. K.

1986-01-01

We assessed renal blood flow and pressor responses to graded angiotensin II doses in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats ingesting a diet containing 1.6% sodium basally and after acute and chronic angiotensin converting enzyme (ACE) inhibition with captopril. In the basal state the pressor response to angiotensin II was enhanced (P<0.0005) and the renal vascular response was blunted (P<0.005) in SHR compared with WKY rats. After acute captopril administration the pressor response was enhanced in both strains, and the difference between them was maintained, while the renal vascular response was enhanced in both, but more in SHR, so that the renal vascular response in the SHR became larger than in WKY (P<0.0001). Chronic captopril treatment blunted both pressor and renal responses in WKY rats, but only the pressor response in SHR. The renal vessels of SHR seem to be different from those of WKY rats in reaction to exogenous angiotensin II, and in response to both acute administration of captopril (probably acting through blockade of angiotensin II production) and chronic administration of captopril (probably acting mainly through accumulation of kinin or production of prostaglandins).

Methylphenidate and Atomoxetine-Responsive Prefrontal Cortical Genetic Overlaps in "Impulsive" SHR/NCrl and Wistar Rats.

PubMed

Dela Peña, Ike; Dela Peña, Irene Joy; de la Peña, June Bryan; Kim, Hee Jin; Shin, Chan Young; Han, Doug Hyun; Kim, Bung-Nyun; Ryu, Jong Hoon; Cheong, Jae Hoon

2017-09-01

Impulsivity, the predisposition to act prematurely without foresight, is associated with a number of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). Identifying genetic underpinnings of impulsive behavior may help decipher the complex etiology and neurobiological factors of disorders marked by impulsivity. To identify potential genetic factors of impulsivity, we examined common differentially expressed genes (DEGs) in the prefrontal cortex (PFC) of adolescent SHR/NCrl and Wistar rats, which showed marked decrease in preference for the large but delayed reward, compared with WKY/NCrl rats, in the delay discounting task. Of these DEGs, we examined drug-responsive transcripts whose mRNA levels were altered following treatment (in SHR/NCrl and Wistar rats) with drugs that alleviate impulsivity, namely, the ADHD medications methylphenidate and atomoxetine. Prefrontal cortical genetic overlaps between SHR/NCrl and Wistar rats in comparison with WKY/NCrl included genes associated with transcription (e.g., Btg2, Fos, Nr4a2), synaptic plasticity (e.g., Arc, Homer2), and neuron apoptosis (Grik2, Nmnat1). Treatment with methylphenidate and/or atomoxetine increased choice of the large, delayed reward in SHR/NCrl and Wistar rats and changed, in varying degrees, mRNA levels of Nr4a2, Btg2, and Homer2, genes with previously described roles in neuropsychiatric disorders characterized by impulsivity. While further studies are required, we dissected potential genetic factors that may influence impulsivity by identifying genetic overlaps in the PFC of "impulsive" SHR/NCrl and Wistar rats. Notably, these are also drug-responsive transcripts which may be studied further as biomarkers to predict response to ADHD drugs, and as potential targets for the development of treatments to improve impulsivity.

Environmental enrichment prevents anxiety-like behavior induced by progesterone withdrawal in two strains of rats.

PubMed

Islas-Preciado, D; López-Rubalcava, C; González-Olvera, J; Gallardo-Tenorio, A; Estrada-Camarena, E

2016-11-12

Stress vulnerability could influence the treatment response to anxiety associated with abrupt hormonal suppression. The present study explored the effects of different treatments on experimental anxiety induced by progesterone withdrawal (PW) in a stress-sensitive rat strain, Wistar Kyoto (WKY), in the burying behavior test (BBT). The following experimental series was conducted using independent groups of Wistar (control strain) and WKY ovariectomized rats: Experiment 1: Rats were treated for 5days with oil, a constant dose of progesterone (0.5mg/rat, s.c) or a combination of progesterone (0.5mg/rat, s.c) plus fluoxetine (10 mg/kg, i.p); on day 6, all rats were subjected to BBT. Experiment 2: Rats received corn oil or decreasing doses of progesterone (0.84, 0.67, 0.5, 0.33 and 0.17mg/rat; one dose daily); on day 6, the rats were subjected to BBT. Experiment 3: Rats were divided into two groups that were subjected to 30days of standard conditions or environmental enrichment (EE); from days 25 to 30, all rats received a fixed dose of progesterone (0.5mg/rat, s.c.) or vehicle. On day 31, the rats were tested with BBT. Results showed that PW increased anxiety in both strains, and fluoxetine prevented anxiety in WKY rats. In contrast, a gradual reduction of progesterone prevents the anxiety in Wistar but not in WKY. EE was preventive against the anxiety induced by PW in both strains of rats. Thus, the results suggest that anxiety induced by PW is prevented by EE while the anxiolytic effect of pharmacological treatments depends on stress vulnerability. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Effect of sympathetic nerves on composition and distensibility of cerebral arterioles in rats.

PubMed Central

Baumbach, G L; Heistad, D D; Siems, J E

1989-01-01

1. The goals of this study were to examine the effects of chronic sympathetic denervation on the mechanics and composition of cerebral arterioles in normotensive Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). 2. We used an in vivo method to examine the mechanics of pial arterioles in 10- to 12-month-old, anaesthetized WKY and SHRSP that had undergone unilateral removal of the superior cervical ganglion at 1 month of age. Bilateral craniotomies were performed in each rat to expose pial arterioles in the innervated and denervated cerebral hemispheres. Arterioles were deactivated with EDTA. Incremental distensibility and stress-strain relationships were calculated from measurements of pial arteriolar pressure (servo null), diameter and cross-sectional area of the arteriolar wall. Point counting stereology was used to quantify volume density and cross-sectional area of individual components in the arteriolar wall. 3. Chronic sympathetic denervation reduced cross-sectional area of the arteriolar wall by 16 +/- 2% (mean +/- S.E. of mean; P less than 0.05) in WKY and 44 +/- 3% in SHRSP. During maximal dilatation with EDTA, incremental distensibility was reduced and the stress-strain curve was shifted to the left in denervated arterioles of SHRSP, but not WKY. These findings indicate that sympathetic denervation in SHRSP attenuates the development of hypertrophy in pial arterioles and reduces arteriolar distensibility. The ratio of non-distensible (collagen and basement membrane) to distensible (smooth muscle, elastin and endothelium) components was reduced in denervated arterioles in SHRSP, but not WKY. 4. Thus, sympathetic nerves have trophic effects on cerebral arterioles in WKY and, to a greater degree, in SHRSP. Sympathetic nerves also contribute to increases in distensibility of cerebral arterioles in SHRSP, but not WKY. The increase in arteriolar distensibility is accompanied by a disproportionate increase in the more compliant

Underexpression of the Na+-dependent neutral amino acid transporter ASCT2 in the spontaneously hypertensive rat kidney.

PubMed

Pinho, Maria João; Pinto, Vanda; Serrão, Maria Paula; Jose, Pedro A; Soares-da-Silva, Patrício

2007-07-01

This study examined the inward transport of l-[(14)C]alanine, an ASCT2 preferential substrate, in monolayers of immortalized renal proximal tubular epithelial (PTE) cells from Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. The expression of ASCT2 in WKY and SHR PTE cells and kidney cortices from WKY and SHR was also evaluated. l-[(14)C]alanine uptake was highly dependent on extracellular Na(+). Replacement of NaCl by LiCl or choline chloride abolished transport activity in SHR and WKY PTE cells. In the presence of the system L inhibitor BCH, Na(+)-dependent l-alanine uptake in WKY and SHR PTE cells was inhibited by alanine, serine, and cysteine, which is consistent with amino acid transport through ASCT2. The saturable component of Na(+)-dependent l-alanine transport under V(max) conditions in SHR PTE cells was one-half of that in WKY PTE cells, with similar K(m) values. Differences in magnitude of Na(+)-dependent l-alanine uptake through ASCT2 between WKY and SHR PTE cells correlated positively with differences in ASCT2 protein expression, this being more abundant in WKY PTE cells. Abundance of ASCT2 transcript and protein in kidney cortices of SHR rats was also lower than that in normotensive WKY rats. In conclusion, immortalized SHR and WKY PTE cells take up l-alanine mainly through a high-affinity Na(+)-dependent amino acid transporter, with functional features of ASCT2 transport. The activity and expression of the ASCT2 transporter were considerably lower in the SHR cells.

Disordered drinking in developing spontaneously hypertensive rats.

PubMed

Kraly, F S; Coogan, L A; Specht, S M; Trattner, M S; Zayfert, C; Cohen, A; Goldstein, J A

1985-04-01

Eating and drinking in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were measured at 5-17 wk of life. The SHR drank significantly more water in 24 h than WKY as early as wk 9, spilled more dry food than did WKY, and exhibited an inverse relation between 24-h water intake and dry food spilled. When eating a meal of dry food after 12 h food deprivation, SHR drank earlier and drank more in a 1-h test than WKY rats. Moreover, SHR exhibited (as early as wk 7) a striking pattern of interrupting eating to drink. This pattern was not present when SHR ate liquid food, and it was attenuated by infusion of water through a cheek fistula. Adult SHR (22 wk) salivated less than WKY in response to intraperitoneal 3.25 mg/kg pilocarpine nitrate. When developing SHR and WKY were maintained on liquid and solid food, SHR gained disproportionately more weight than WKY during development. When young SHR were permitted to drink no more water than WKY rats, the development of hypertension was retarded, and body weight gain was slowed. Because restricted access to food, which produced an equivalent slowing of body weight gain as did restricted access to water, also retarded development of hypertension, it appears that restricted access to water retards development of hypertension due to delayed growth. These results demonstrate that hyperdipsia, apparently caused by deficient salivary function, is not necessary for the development of hypertension in SHR.

Quinapril decreases myocardial accumulation of extracellular matrix components in spontaneously hypertensive rats.

PubMed

Panizo, A; Pardo, J; Hernández, M; Galindo, M F; Cenarruzabeitia, E; Díez, J

1995-08-01

In genetic and acquired hypertension, a structural remodeling of the nonmyocyte compartment of myocardium, including the accumulation of fibrillar collagen and other components of the extracellular matrix (ECM) within the interstitium, represents a determinant of pathologic hypertrophy that leads to ventricular dysfunction. Therefore, to evaluate the potential benefit of the angiotensin converting enzyme (ACE) inhibitor quinapril in reversing the interstitial remodeling in spontaneously hypertensive rats (SHR) with established left ventricular hypertrophy (LVH), we treated 16-week-old male SHR with oral quinapril (average dose, 10 mg/kg body weight/day) for 20 weeks. Interstitial fibrosis was determined morphometrically using an automatic image analyzer. The amount of collagen was evaluated by measuring myocardial hydroxyproline concentration. Myocardial deposition of collagen molecules (types I, III, and IV) and other ECM components (fibronectin, laminin) was analyzed by immunohistochemical techniques using specific monoclonal antibodies. The activity of ACE was measured in left ventricular tissue by a fluorometric assay. In quinapril-treated SHR compared with 36-week-old untreated SHR and age- and sex-matched Wistar-Kyoto (WKY) controls, we found 1) a lesser degree of LVH and a lesser level of blood pressure, 2) a lesser degree of interstitial fibrosis, represented by less interstitial collagen volume fraction (5.73 +/- 0.45% v 3.42 +/- 0.28%, P < .05; WKY, 3.44 +/- 0.66%), 3) a lower hydroxyproline concentration (1.09 +/- 0.05 mumol/L/g dry weight/100 g body weight to 0.81 +/- 0.05 mumol/L/g dry weight/100 g body weight, P < .05; WKY, 0.96 +/- 0.06 mumol/L/g dry weight/100 g body weight), 4) a lesser presence of collagen fibers, and 5) a lesser presence of collagen IV, fibronectin, and laminin.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of genetic strain on body fat loss, food consumption, metabolism, ventilation, and motor activity in free running female rats.

PubMed

Gordon, C J; Phillips, P M; Johnstone, A F M

2016-01-01

Chronic exercise is considered as one of the most effective means of countering symptoms of the metabolic syndrome (MS) such as obesity and hyperglycemia. Rodent models of forced or voluntary exercise are often used to study the mechanisms of MS and type 2 diabetes. However, there is little known on the impact of genetic strain on the metabolic response to exercise. We studied the effects of housing rats with running wheels (RW) for 65 days compared to sedentary (SED) housing in five female rat strains: Sprague-Dawley (SD), Long-Evans (LE), Wistar (WIS), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY). Key parameters measured were total distance run, body composition, food consumption, motor activity, ventilatory responses by plethysmography, and resting metabolic rate (MR). WKY and SHR ran significantly more than the WIS, LE, and SD strains. Running-induced reduction in body fat was affected by strain but not by distance run. LE's lost 6% fat after 21 d of running whereas WKY's lost 2% fat but ran 40% more than LE's. LE and WIS lost body weight while the SHR and WKY strains gained weight during running. Food intake with RW was markedly increased in SHR, WIS, and WKY while LE and SD showed modest increases. Exploratory motor activity was reduced sharply by RW in all but the SD strain. Ventilatory parameters were primarily altered by RW in the SHR, WKY, and WIS strains. MR was unaffected by RW. In an overall ranking of physiological and behavioral responses to RW, the SD strain was considered the least responsive whereas the WIS was scored as most responsive. In terms of RW-induced fat loss, the LE strain appears to be the most ideal. These results should be useful in the future selection of rat models to study benefits of volitional exercise. Published by Elsevier Inc.

Pathological effects of obstructive apneas during the sleep cycle in an animal model of cerebral small vessel disease.

PubMed

Lloyd, Eric E; Durgan, David J; Martini, Sharyl R; Bryan, Robert M

2015-10-01

We tested the hypothesis that apneas during the sleep cycle exacerbate hypertension and accelerate changes that occur with cerebral small vessel disease. Obstructive sleep apnea was modeled by intermittent inflations of a chronically implanted tracheal balloon to occlude the airway during the sleep cycle (termed OSA) in spontaneously hypertensive stroke-prone (SHRSP) rats, a model of cerebral small vessel disease. SHRSP rats and their parent strain, Wistar Kyoto (WKY) rats, were exposed to OSA for 2 weeks (from 9 to 11 or from 18 to 20 weeks). At 9 weeks, hypertension was developing in the SHRSP rats and was firmly established by 18 weeks. OSA exposure increased systolic blood pressure in SHRSP rats by ≈30 mm Hg in both age groups compared with shams that were surgically prepared but not exposed to OSA (P<0.05). OSA exposure also increased systolic blood pressure in WKY rats by 20 and 37 mm Hg at 11 and 20 weeks, respectively (P<0.05). OSA exposure in SHRSP rats compromised blood-brain barrier integrity in white matter at both 11 and 20 weeks of age when compared with SHRSP sham rats (P<0.05). Microglia were activated in SHRSP rats exposed to OSA but not in sham rats at 11 weeks (P<0.05). At 20 weeks, microglia were activated in sham SHRSP rats (P<0.05) compared with WKY sham rats and were not further activated by OSA. Neither was blood-brain barrier integrity altered nor microglia activated in any of the WKY groups. We conclude that OSA accelerates the onset of the cerebral pathologies associated with cerebral small vessel disease in SHRSP, but not WKY, rats. © 2015 American Heart Association, Inc.

Performance on a strategy set shifting task during adolescence in a genetic model of attention deficit/hyperactivity disorder: Methylphenidate vs. atomoxetine treatments

PubMed Central

Harvey, Roxann C; Jordan, Chloe J; Tassin, David H; Moody, Kayla R; Dwoskin, Linda P; Kantak, Kathleen M

2013-01-01

Research examining medication effects on set shifting in teens with attention deficit/hyperactivity disorder (ADHD) is lacking. An animal model of ADHD may be useful for exploring this gap. The Spontaneously Hypertensive Rat (SHR) is a commonly used animal model of ADHD. SHR and two comparator strains, Wistar-Kyoto (WKY) and Wistar (WIS), were evaluated during adolescence in a strategy set shifting task under conditions of a 0-sec or 15-sec delay to reinforcer delivery. The task had three phases: initial discrimination, set shift and reversal learning. Under 0-sec delays, SHR performed as well as or better than WKY and WIS. Treatment with 0.3 mg/kg/day atomoxetine had little effect, other than to modestly increase trials to criterion during set shifting in all strains. Under 15-sec delays, SHR had longer lever press reaction times, longer latencies to criterion and more trial omissions than WKY during set shifting and reversal learning. These deficits were not reduced systematically by 1.5 mg/kg/day methylphenidate or 0.3 mg/kg/day atomoxetine. Regarding learning in SHR, methylphenidate improved initial discrimination, whereas atomoxetine improved set shifting but disrupted initial discrimination. During reversal learning, both drugs were ineffective in SHR, and atomoxetine made reaction time and trial omissions greater in WKY. Overall, WIS performance differed from SHR or WKY, depending on phase. Collectively, a genetic model of ADHD in adolescent rats revealed that neither methylphenidate nor atomoxetine mitigated all deficits in SHR during the set shifting task. Thus, methylphenidate or atomoxetine monotherapy may not mitigate all set shift task-related deficits in teens with ADHD. PMID:23376704

Vascular smooth muscle cell polyploidy and cardiomyocyte hypertrophy due to chronic NOS inhibition in vivo.

PubMed

Devlin, A M; Brosnan, M J; Graham, D; Morton, J J; McPhaden, A R; McIntyre, M; Hamilton, C A; Reid, J L; Dominiczak, A F

1998-01-01

To assess the vascular and cardiac response to NO (nitric oxide) synthase (NOS) blockade in vivo, Wistar-Kyoto rats (WKY) were treated for 3 wk with NG-nitro-L-arginine methyl ester (L-NAME; 10 mg.kg-1.day-1). L-NAME treatment induced hypertension that was associated with increased plasma renin activity. Flow cytometry cell cycle DNA analysis showed that aortic vascular smooth muscle cells (VSMC) from L-NAME-treated WKY had a significantly higher polyploid population compared with WKY controls. Using organ bath experiments, we have shown that aortic rings from L-NAME-treated WKY have an increased contractile response to phenylephrine and impaired relaxation to carbachol compared with control rings. NOS blockade in vivo caused a significant increase in cardiac and left ventricular hypertrophy. Northern mRNA analysis of the myocardium showed that L-NAME treatment caused reexpression of the fetal skeletal alpha-actin isoform without alterations in collagen type I expression, a pattern indicating true hypertrophy of the cardiomyocytes. These studies provide further insight to confirm that NO deficiency in vivo results in the development of vascular and cardiac hypertrophy.

Central N-acetylcysteine effects on baroreflex in juvenile spontaneously hypertensive rats.

PubMed

Valenti, Vitor E; De Abreu, Luiz Carlos; Sato, Monica A; Saldiva, Paulo H N; Fonseca, Fernando L A; Giannocco, Gisele; Riera, Andreas R P; Ferreira, Celso

2011-06-01

In this study, we evaluated the acute effects of central NAC administration on baroreflex in juvenile SHR and Wistar Kyoto (WKY) rats. Male SHR and WKY rats (8-10 weeks old) were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. After basal MAP and HR recordings, the baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 μg/kg, bolus) and a depressor dose of sodium nitroprusside (SNP, 50 μg/kg, bolus). Baroreflex was evaluated before, 5, 15, 30 and 60 minutes after NAC injection into the 4th V. Vehicle treatment did not change baroreflex responses in WKY and SHR. Central NAC slightly but significantly increased basal HR at 15 minutes and significantly reduced PHE-induced increase in MAP 30 and 60 minutes after NAC injection (p < 0.05) in WKY rats. In relation to SHR, NAC decreased HR range 15 and 30 minutes after its administration. In conclusion, acute NAC into the 4th V does not improve baroreflex in juvenile SHR.

Differential use of danger and safety signals in an animal model of anxiety vulnerability: The behavioral economics of avoidance.

PubMed

Spiegler, Kevin M; Fortress, Ashley M; Pang, Kevin C H

2018-03-02

Differential processing of danger and safety signals may underlie symptoms of anxiety disorders and posttraumatic stress disorder. One symptom common to these disorders is pathological avoidance. The present study examined whether danger and safety signals influence avoidance differently in anxiety-vulnerable Wistar-Kyoto (WKY) rats and Sprague Dawley (SD) rats. SD and WKY rats were tested in a novel progressive ratio avoidance task with and without danger or safety signals. Two components of reinforcement, hedonic value and motivation, were determined by fitting an exponentiated demand equation to the data. Hedonic value of avoidance did not differ between SD and WKY rats, but WKY rats had greater motivation to avoid than SD rats. Removal of the safety signal reduced motivation to avoid in SD, but not WKY, rats. Removal of the danger signal did not alter avoidance in either strain. When danger and safety signals were presented simultaneously, WKY rats responded to the danger signals, whereas SD rats responded to the safety signal. The results provide evidence that 1) safety signals enhance motivation to avoid in SD rats, 2) both danger and safety signals influence motivation in WKY rats, and 3) danger signals take precedence over safety signals when presented simultaneously in WKY rats. Thus, anxiety vulnerability is associated with preferential use of danger signals to motivate avoidance. The differential use of danger and safety signals has important implications for the etiology and treatment of pathological avoidance in anxiety disorders and posttraumatic stress disorder. Copyright © 2017. Published by Elsevier Inc.

A microstructural analysis of schedule-induced polydipsia reveals incentive-induced hyperactivity in an animal model of ADHD

PubMed Central

Íbias, Javier; Pellón, Ricardo; Sanabria, Federico

2014-01-01

Recent research has suggested that frequent short bursts of activity characterize hyperactivity associated with attention deficit hyperactivity disorder (ADHD). This study determined whether such pattern is also visible in schedule-induced polydipsia (SIP) in the spontaneously hypertensive rat (SHR), an animal model of ADHD. Male SHR, Wistar Kyoto (WKY) and Wistar rats were exposed to 40 sessions of SIP using a multiple fixed-time (FT) schedule of food delivery with FT 30-s and FT 90-s components. Stable performance was analysed to determine the extent to which SIP-associated drinking is organized in bouts. The Bi-Exponential Refractory Model (BERM) of free-operant performance was applied to schedule-induced licks. A model comparison analysis supported BERM as a description of SIP episodes: licks were not produced at a constant rate but organized into bouts within drinking episodes. FT 30-s induced similar overall licking rates, latencies to first licks and episode durations across strains; FT 90-s induced longer episode durations in SHRs and reduced licking rate in WKY and Wistar rats to nearly baseline levels. Across schedules, SHRs made more and shorter bouts when compared to the other strains. These results suggest an incentive-induced hyperactivity in SHR that has been observed in operant behavior and in children with ADHD. PMID:25447297

Chronic type 1 diabetes in spontaneously hypertensive rats leads to exacerbated cardiac fibrosis.

PubMed

Black, Mary Jane; D'Amore, Angelo; Auden, Alana; Stamp, Laura; Osicka, Tanya; Panagiotopoulos, Sianna; Jerums, George

2010-01-01

Diabetes in human subjects is often associated with hypertension. The aim of this study was to examine the development of cardiac fibrosis following induction of type 1 diabetes in genetically hypertensive rats. Diabetes was induced by streptozotocin (STZ) injection in 8-week-old normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) for a duration of 16 or 24 weeks. Aged-matched, nondiabetic WKY and SHRs were used as controls. At termination of treatment, the rats were anaesthetized, hearts arrested in diastole and perfusion fixed. A comprehensive examination of cardiac fibrosis throughout the right and left ventricles was undertaken in picrosirius red-stained sections, using image analysis and by undertaking collagen type I and type III immunohistochemistry. Induction of diabetes in the SHRs led to a marked increase in the levels of interstitial fibrosis in the left ventricle plus septum (LV+S) at both 16 and 24 weeks duration (59% and 43% increase, respectively) and also in the right ventricle after 24 weeks duration of diabetes (35% increase compared to the nondiabetic SHR). Exacerbated perivascular fibrosis was also observed in the LV+S in the diabetic-hypertensive rats at the later time point. These effects of induction of diabetes were not observed in the normotensive strain. Our findings clearly demonstrate elevations in cardiac fibrosis when type 1 diabetes is combined with hypertension. Our findings thus stress the importance of closely monitoring both blood pressure and glucose levels in type 1 diabetic patients in order to prevent myocardial collagen deposition. Copyright © 2010 Elsevier Inc. All rights reserved.

Specific growth stimulation of cultured smooth muscle cells from spontaneously hypertensive rats by platelet-derived growth factor A-chain homodimer.

PubMed Central

Resink, T J; Scott-Burden, T; Hahn, A W; Rouge, M; Hosang, M; Powell, J S; Bühler, F R

1990-01-01

Cultured vascular smooth muscle cells (VSMC)1 from spontaneously hypertensive rats (SHR) possess specific cell surface receptors for both homodimeric forms of platelet-derived growth factor (PDGF-AA and PDGF-BB), in contrast to cells from normotensive Wistar Kyoto (WKY) animals, which express receptors only for the B-chain form of PDGF. Stimulation of quiescent VSMC from SHR with PDGF-AA resulted in activation of S6-kinase and induction of phosphoinositide catabolism, as well as cellular proliferation when cultures were maintained for prolonged periods with daily supplementation of the growth factor. WKY-derived VSMC showed no response to PDGF-AA, which was consistent with their lack of specific receptors for this homodimer. The responsiveness of quiescent cells from SHR and WKY to the B-chain homodimer was similar. The enhanced growth responsiveness of SHR-derived cells to fetal calf serum, as compared with cells from their normotensive counterparts, may be accounted for in part by their expression of receptors for the AA homodimer of PDGF. PMID:1965150

Effect of deuterium-depleted water on selected cardiometabolic parameters in fructose-treated rats.

PubMed

Rehakova, R; Klimentova, J; Cebova, M; Barta, A; Matuskova, Z; Labas, P; Pechanova, O

2016-10-24

Deuterium-depleted water (DDW) has a lower concentration of deuterium than occurs naturally (less than 145 ppm). While effects of DDW on cancer started to be intensively studied, the effects on cardiovascular system are completely unknown. Thus, we aimed to analyze the effects of DDW (55+/-5 ppm) administration to 12-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) treated with 15 % fructose for 6 weeks. Blood pressure (BP) and selected biochemical parameters were measured together with determination of nitric oxide synthase (NOS) activity and iNOS and eNOS protein expressions in the left ventricle (LV) and aorta. Neither DDW nor fructose had any significant effect on BP in both strains. DDW treatment decreased total cholesterol and triglyceride levels in WKY, but it was not able to prevent increase in the same parameters elevated due to fructose treatment in SHR. Both fructose and DDW increased insulin level in WKY. Fructose did not affect NOS activity either in WKY or SHR. DDW increased NOS activity in LV of both WKY and SHR, while it decreased NOS activity and iNOS expression in the aorta of SHR with or without fructose treatment. In conclusion, DDW treatment significantly modified biochemical parameters in WKY together with NOS activity elevation in the heart. On the other hand, it did not affect biochemical parameters in SHR, but decreased NOS activity elevated due to iNOS upregulation in the aorta.

Renal mechanoreceptor dysfunction: an intermediate phenotype in spontaneously hypertensive rats.

PubMed

DiBona, G F; Jones, S Y; Kopp, U C

1999-01-01

This study tested the hypothesis that decreased responsiveness of renal mechanosensitive neurons constitutes an intermediate phenotype in spontaneously hypertensive rats (SHR). Decreased responsiveness of these sensory neurons would contribute to increased renal sympathetic nerve activity and sodium retention, characteristic findings in hypertension. A backcross population, developed by mating borderline hypertensive rats with Wistar-Kyoto rats (WKY) (the F1 of a cross between an SHR and a normotensive WKY), was fed 8% NaCl food for 12 weeks from age 4 to 16 weeks. Responses to increases in ureteral pressure to 20 and 40 mm Hg in 80 backcross rats instrumented for measurement of mean arterial pressure and afferent renal nerve activity were determined. Mean arterial pressure ranged from 110 to 212 mm Hg and was inversely correlated with the magnitude of the increase in afferent renal nerve activity during increased ureteral pressure. Thus, decreased responsiveness of renal mechanosensitive neurons cosegregated with hypertension in this backcross population. This aspect of the complex quantitative trait of altered renal sympathetic neural control of renal function, ie, decreased renal mechanoreceptor responsiveness, is part of an intermediate phenotype in SHR.

Prenatal and early postnatal dietary sodium restriction sensitizes the adult rat to amphetamines.

PubMed

McBride, Shawna M; Culver, Bruce; Flynn, Francis W

2006-10-01

Acute sodium deficiency sensitizes adult rats to psychomotor effects of amphetamine. This study determined whether prenatal and early life manipulation of dietary sodium sensitized adult offspring to psychomotor effects of amphetamine (1 or 3 mg/kg ip) in two strains of rats. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) dams were fed chow containing low NaCl (0.12%; LN), normal NaCl (1%; NN), or high NaCl (4%; HN) throughout breeding, gestation, and lactation. Male offspring were maintained on the test diet for an additional 3 wk postweaning and then fed standard chow thereafter until testing began. Overall, blood pressure (BP), total fluid intake, salt preference, and adrenal gland weight were greater in SHR than in WKY. WKY LN offspring had greater water intake and adrenal gland weight than did WKY NN and HN offspring, whereas WKY HN offspring had increased BP, salt intake, and salt preference compared with other WKY offspring. SHR HN offspring also had increased BP compared with other SHR offspring; all other measures were similar for SHR offspring. The low-dose amphetamine increased locomotor and stereotypical behavior compared with baseline and saline injection in both WKY and SHR offspring. Dietary sodium history affected the rats' psychomotor response to the higher dose of amphetamine. Injections of 3 mg/kg amphetamine in both strains produced significantly more behavioral activity in the LN offspring than in NN and HN offspring. These results show that early life experience with low-sodium diets produce long-term changes in adult rats' behavioral responses to amphetamine.

Ozone-Induced Metabolic Impairment is Attenuated in Adrenalectomized Wistar Kyoto Rats

EPA Science Inventory

Rationale: Air pollutants have been linked to increased incidence of metabolic syndrome however the mechanisms are poorly understood. We have recently shown that ozone exposure induces significant hyperglycemia together with elevated serum leptin and epinephrine in the Wistar Ky...

Stimulus Processing and Associative Learning in Wistar and WKHA Rats

PubMed Central

Chess, Amy C.; Keene, Christopher S.; Wyzik, Elizabeth C.; Bucci, David J.

2007-01-01

This study assessed basic learning and attention abilities in WKHA (Wistar-Kyoto Hyperactive) rats using appetitive conditioning preparations. Two measures of conditioned responding to a visual stimulus, orienting behavior (rearing on the hindlegs) and food cup behavior (placing the head inside the recessed food cup) were measured. In Experiment 1, simple conditioning but not extinction was impaired in WKHA rats compared to Wistar rats. In Experiment 2, non-reinforced presentations of the visual cue preceded the conditioning sessions. WKHA rats displayed less orienting behavior than Wistar rats, but comparable levels of food cup behavior. These data suggest that WKHA rats exhibit specific abnormalities in attentional processing as well as learning stimulus-reward relationships. PMID:15998198

Enhanced expression of Gqα and PLC-β1 proteins contributes to vascular smooth muscle cell hypertrophy in SHR: role of endogenous angiotensin II and endothelin-1.

PubMed

Atef, Mohammed Emehdi; Anand-Srivastava, Madhu B

2014-07-01

Vascular Gqα signaling has been shown to contribute to cardiac hypertrophy. In addition, angiotensin II (ANG II) was shown to induce vascular smooth muscle cell (VSMC) hypertrophy through Gqα signaling; however, the studies on the role of Gqα and PLC-β1 proteins in VSMC hypertrophy in animal model are lacking. The present study was therefore undertaken to examine the role of Gqα/PLC-β1 proteins and the signaling pathways in VSMC hypertrophy using spontaneously hypertensive rats (SHR). VSMC from 16-wk-old SHR and not from 12-wk-old SHR exhibited enhanced levels of Gqα/PLC-β1 proteins compared with age-matched Wistar-Kyoto (WKY) rats as determined by Western blotting. However, protein synthesis as determined by [(3)H]leucine incorporation was significantly enhanced in VSMC from both 12- and 16-wk-old SHR compared with VSMC from age-matched WKY rats. Furthermore, the knockdown of Gqα/PLC-β1 in VSMC from 16-wk-old SHR by antisense and small interfering RNA resulted in attenuation of protein synthesis. In addition, the enhanced expression of Gqα/PLC-β1 proteins, enhanced phosphorylation of ERK1/2, and enhanced protein synthesis in VSMC from SHR were attenuated by the ANG II AT1 and endothelin-1 (ET-1) ETA receptor antagonists losartan and BQ123, respectively, but not by the ETB receptor antagonist BQ788. In addition, PD98059 decreased the enhanced expression of Gqα/PLC-β1 and protein synthesis in VSMC from SHR. These results suggest that the enhanced levels of endogenous ANG II and ET-1 through the activation of AT1 and ETA receptors, respectively, and MAP kinase signaling, enhanced the expression of Gqα/PLC-β1 proteins in VSMC from 16-wk-old SHR and result in VSMC hypertrophy. Copyright © 2014 the American Physiological Society.

A microstructural analysis of schedule-induced polydipsia reveals incentive-induced hyperactivity in an animal model of ADHD.

PubMed

Íbias, Javier; Pellón, Ricardo; Sanabria, Federico

2015-02-01

Recent research has suggested that frequent short bursts of activity characterize hyperactivity associated with attention deficit hyperactivity disorder (ADHD). This study determined whether such pattern is also visible in schedule-induced polydipsia (SIP) in the spontaneously hypertensive rat (SHR), an animal model of ADHD. Male SHR, Wistar Kyoto (WKY) and Wistar rats were exposed to 40 sessions of SIP using a multiple fixed-time (FT) schedule of food delivery with FT 30-s and FT 90-s components. Stable performance was analyzed to determine the extent to which SIP-associated drinking is organized in bouts. The Bi-Exponential Refractory Model (BERM) of free-operant performance was applied to schedule-induced licks. A model comparison analysis supported BERM as a description of SIP episodes: licks were not produced at a constant rate but organized into bouts within drinking episodes. FT 30-s induced similar overall licking rates, latencies to first licks and episode durations across strains; FT 90-s induced longer episode durations in SHRs and reduced licking rate in WKY and Wistar rats to nearly baseline levels. Across schedules, SHRs made more and shorter bouts when compared to the other strains. These results suggest an incentive-induced hyperactivity in SHR that has been observed in operant behaviour and in children with ADHD. Copyright © 2014 Elsevier B.V. All rights reserved.

Ketamine facilitates extinction of avoidance behavior and enhances synaptic plasticity in a rat model of anxiety vulnerability: Implications for the pathophysiology and treatment of anxiety disorders.

PubMed

Fortress, Ashley M; Smith, Ian M; Pang, Kevin C H

2018-05-08

Anxiety disorders and posttraumatic stress disorder (PTSD) share a common feature of pathological avoidance behavior. The Wistar Kyoto (WKY) rat has been used as a model of anxiety vulnerability, expressing a behaviorally inhibited temperament, acquiring avoidance behavior more rapidly and displaying extinction-resistant avoidance compared to Sprague Dawley (SD) rats. Subanesthetic levels of ketamine have gained attention as a rapid antidepressant in treatment-resistant depression. While traditional antidepressants are commonly used to treat anxiety disorders and PTSD, the therapeutic utility of ketamine for these disorders is much less understood. The hippocampus is critical for the actions of antidepressants, is a structure of implicated in anxiety disorders and PTSD, and is necessary for extinction of avoidance in SD rats. WKY rats have impaired hippocampal long-term potentiation (LTP), suggesting that persistent avoidance in WKY rats may be due to deficient hippocampal synaptic plasticity. In the present study, we hypothesized that ketamine would facilitate extinction of avoidance learning in WKY rats, and do so by enhancing hippocampal synaptic plasticity. As predicted, ketamine facilitated extinction of avoidance behavior in a subset of WKY rats (responders), with effects lasting at least three weeks. Additionally, LTP in these rats was enhanced by ketamine. Ketamine was not effective in facilitating avoidance extinction or in modifying LTP in WKY non-responders. The results suggest that subanesthetic levels of ketamine may be useful for treating anxiety disorders by reducing avoidance behaviors when combined with extinction conditions. Moreover, ketamine may have its long-lasting behavioral effects through enhancing hippocampal synaptic plasticity. Copyright © 2018. Published by Elsevier Ltd.

DIFFERENTIAL CARDIAC SUSCEPTIBILITY OF WISTAR KYOTO (WKY) AND SPONTANEOUSLY HYPERTENSIVE RATS (SHR) TO DIESEL EXHAUST EXPOSURE

EPA Science Inventory

Exposure to diesel exhaust particles (DEP) is linked to increases in cardiovascular effects. This is enhanced in individuals with pre-existing disease. Animal models of cardiovascular disease are used to study this susceptibility. The heart is rich in mitochondria, which produce ...

Oxotremorine-induced cerebral hyperemia does not predict infarction volume in spontaneously hypertensive or stroke-prone rats.

PubMed

Harukuni, I; Takahashi, H; Traystman, R J; Bhardwaj, A; Kirsch, J R

2000-01-01

We tested the following hypotheses: a) spontaneously hypertensive stroke-prone rats (SHR-SP) have more brain injury than spontaneously hypertensive rats (SHR) and normotensive controls (Wistar-Kyoto rats [WKY]) when exposed to transient focal ischemia; b) infarction size is not correlated with baseline blood pressure; and c) infarction size is inversely related to the cerebral hyperemic response to oxotremorine, a muscarinic agonist that increases cerebral blood flow (CBF) by stimulating endothelial nitric oxide synthase. In vivo study. Animal laboratory in a university teaching hospital. Adult age-matched male WKY, SHR, and SHR-SP. Rats were instrumented under halothane anesthesia. Transient focal cerebral ischemia was produced for 2 hrs with the intravascular suture technique. Cerebral perfusion, estimated with laser Doppler flowmetry (LD-CBF), in response to intravenous oxotremorine, was measured in one cohort of rats to estimate endothelial nitric oxide synthase function. Infarction volume was measured at 22 hrs of reperfusion with 2,3,5-triphenyltetrazolium chloride staining. Infarction volume in the striatum of SHR-SP (42+/-4 mm3) was greater than in SHR (29+/-6 mm3) or WKY (1+/-1 mm3) (n = 9 rats/strain). Resting (unanesthetized) mean arterial blood pressure was similar in SHR-SP (177+/-5 mm Hg) and SHR (170+/-5 mm Hg) despite a greater infarction volume in SHR-SP (n = 4) compared with SHR (n = 5). The percentage increase in LD-CBF signal in response to oxotremorine was similar for both groups (SHR, 64%+/-22% [n = 10]; SHR-SP, 69%+/-22% [n = 8]). However, in this cohort, cortical infarction volume was less in SHR (30%+/-4% of ipsilateral cortex) than in SHR-SP (49%+/-2% of ipsilateral cortex). Although SHR-SP have greater infarction volume than SHR, the mechanism of injury does not appear to be related to a difference in unanesthetized baseline mean arterial blood pressure or to an alteration in endothelium-produced nitric oxide.

Enhanced 5-hydroxytryptamine (5-HT) release from vascular adrenergic nerves in spontaneously hypertensive rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawasaki, H.; Urabe, M.; Takasaki, K.

1986-03-01

The release of 5-HT from vascular adrenergic nerves was compared between normotensive Wistar Kyoto rats (WKY) and SHR. The mesenteric vascular bed isolated from WKY and SHR was perfused with Krebs solution at a constant flow rate of 5 ml/min. Periarterial nerve stimulation (PNS) was delivered at 4 to 16 Hz for 30 sec. In the SHR preparation, the pressor response to PNS, previously decreased by prazonsin (50 nM), was greatly potentiated after treatment with 5-HT(1 ..mu..M) for 15 min and a frequency-dependent pressor response to PNS reappeared, whereas the 5-HT treatment did not alter the pressor response to exogenousmore » norepinephrine (1 nmol) previously reduced by prazonsin. The potentiation of pressor response to PNS after 5-HT treatment was small in the WKY preparation. This potentiation in both WKY and SHR did not occur in the presence of ketanserin (10 nM). In the preparation labeled with (/sup 3/H)-5-HT, PNS (4-16 Hz) evoked a frequency-dependent increase of (/sup 3/H)-efflux, which was abolished by treatment with tetrodotoxin (100 nM) or 6-hydroxydopamine (50 mg/kg i.p. x 2) and in calcium-free Krebs solution. The PNS evoked-(/sup 3/H)-efflux was much greater in SHR than WKY. These results suggest that the release of 5-HT from vascular adrenergic nerves by PNS is enhanced in the SHR preparation.« less

Molecular basis for impaired collateral artery growth in the spontaneously hypertensive rat: insight from microarray analysis

PubMed Central

Unthank, Joseph L; McClintick, Jeanette N; Labarrere, Carlos A; Li, Lang; DiStasi, Matthew R; Miller, Steven J

2013-01-01

Analysis of global gene expression in mesenteric control and collateral arteries was used to investigate potential molecules, pathways, and mechanisms responsible for impaired collateral growth in the Spontaneously Hypertensive Rat (SHR). A fundamental difference was observed in overall gene expression pattern in SHR versus Wistar Kyoto (WKY) collaterals; only 6% of genes altered in collaterals were similar between rat strains. Ingenuity® Pathway Analysis (IPA) identified major differences between WKY and SHR in networks and biological functions related to cell growth and proliferation and gene expression. In SHR control arteries, several mechano-sensitive and redox-dependent transcription regulators were downregulated including JUN (−5.2×, P = 0.02), EGR1 (−4.1×, P = 0.01), and NFĸB1 (−1.95×, P = 0.04). Predicted binding sites for NFĸB and AP-1 were present in genes altered in WKY but not SHR collaterals. Immunostaining showed increased NFĸB nuclear translocation in collateral arteries of WKY and apocynin-treated SHR, but not in untreated SHR. siRNA for the p65 subunit suppressed collateral growth in WKY, confirming a functional role of NFkB. Canonical pathways identified by IPA in WKY but not SHR included nitric oxide and renin–angiotensin system signaling. The angiotensin type 1 receptor (AGTR1) exhibited upregulation in WKY collaterals, but downregulation in SHR; pharmacological blockade of AGTR1 with losartan prevented collateral luminal expansion in WKY. Together, these results suggest that collateral growth impairment results from an abnormality in a fundamental regulatory mechanism that occurs at a level between signal transduction and gene transcription and implicate redox-dependent modulation of mechano-sensitive transcription factors such as NFĸB as a potential mechanism. PMID:24303120

Genetically determined differences in noradrenergic function: The spontaneously hypertensive rat model.

PubMed

Sterley, Toni-Lee; Howells, Fleur M; Russell, Vivienne A

2016-06-15

While genetic predisposition is a major factor, it is not known how development of attention-deficit/hyperactivity disorder (ADHD) is modulated by early life stress. The spontaneously hypertensive rat (SHR) displays the behavioral characteristics of ADHD (poorly sustained attention, impulsivity, hyperactivity) and is the most widely studied genetic model of ADHD. We have previously shown that SHR have disturbances in the noradrenergic system and that the early life stress of maternal separation failed to produce anxiety-like behavior in SHR, contrary to control Sprague-Dawley and Wistar-Kyoto (WKY) who showed typical anxiety-like behavior in later life. In the present study we investigated the effect of maternal separation on approach behavior (response to a novel object in a familiar environment) in preadolescent SHR and WKY. We also investigated whether maternal separation altered GABAA and NMDA receptor-mediated regulation of norepinephrine release in preadolescent SHR and WKY hippocampus. We found that female SHR, similar to male SHR, exhibited greater exploratory activity than WKY. Maternal separation significantly increased GABAA receptor-mediated inhibition of glutamate-stimulated release of norepinephrine in male and female SHR hippocampus but had no significant effect in WKY. Maternal separation had opposite effects on NMDA receptor-mediated inhibition of norepinephrine release in SHR and WKY hippocampus, as it increased inhibition of both glutamate-stimulated and depolarization-evoked release in SHR hippocampus but not in WKY. The results of the present study show that noradrenergic function is similarly altered by the early life stress of maternal separation in male and female SHR, while GABA- and glutamate-regulation of norepinephrine release remained unaffected by maternal separation in the control, WKY, rat strain. This article is part of a Special Issue entitled SI: Noradrenergic System. Copyright © 2015 Elsevier B.V. All rights reserved.

Time course of hyperosmolar opening of the blood-brain and blood-CSF barriers in spontaneously hypertensive rats.

PubMed

Al-Sarraf, Hameed; Ghaaedi, Firuz; Redzic, Zoran

2007-01-01

The time course of blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) responses to hyperosmolar mannitol infusion (HMI; 1.6 M) during chronic hypertension was investigated using (14)C-sucrose as a marker of barrier integrity. (14)C-sucrose entry into CSF of both spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats 2 min after HMI increased approximately 7-fold compared to their respective control. The volume of distribution (V(d)) of (14)C-sucrose into brain cortex of SHR increased 13-fold 2 min after HMI while that in WKY rats increased only 4-fold. After HMI V(d) of (14)C-sucrose into the cortex of WKY, and CSF of both SHR and WKY remained steadily greater than their corresponding control for up to 30 min (p < 0.01), whereas in the cortex of SHR the V(d) of (14)C-sucrose reached control values 20 min after HMI (p > 0.05), indicating that after HMI the increase in paracellular diffusion of (14)C-sucrose into SHR cortex was not persistent, in contrast to WKY rats and CSF of both SHR and WKY rats. Electron microscopy of the brain cortex after HMI showed capillary endothelial cell shrinkage and perivascular swellings in the brain cortex, and in the choroid plexus opening of tight junctions were observed. Our results indicate disruption of both the BBB and the BCSFB after HMI in both SHR and WKY rats. The disruption remained persistent up to 25 min after HMI at the BBB of WKY rats and BCSFB in both animal groups, while in SHR the protective function of the BBB returned to control values 20 min after HMI. Copyright 2007 S. Karger AG, Basel.

Vascular effects of the Mangifera indica L. extract (Vimang).

PubMed

Beltrán, Amada E; Alvarez, Yolanda; Xavier, Fabiano E; Hernanz, Raquel; Rodriguez, Janet; Núñez, Alberto J; Alonso, María J; Salaices, Mercedes

2004-09-24

The effects of the Mangiferia indica L. (Vimang) extract, and mangiferin (a C-glucosylxanthone of Vimang) on the inducible isoforms of cyclooxygenase (cyclooxygenase-2) and nitric oxide synthase (iNOS) expression and on vasoconstrictor responses were investigated in vascular smooth muscle cells and mesenteric resistance arteries, respectively, from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Vimang (0.5-0.1 mg/ml) and mangiferin (0.025 mg/ml) inhibited the interleukin-1beta (1 ng/ml)-induced iNOS expression more in SHR than in WKY, and cyclooxygenase-2 expression more in WKY than in SHR. Vimang (0.25-1 mg/ml) reduced noradrenaline (0.1-30 microM)- and U46619 (1 nM-30 microM)- but not KCl (15-70 mM)-induced contractions. Mangiferin (0.05 mg/ml) did not affect noradrenaline-induced contraction. In conclusion, the antiinflammatory action of Vimang would be related with the inhibition of iNOS and cyclooxygenase-2 expression, but not with its effect on vasoconstrictor responses. Alterations in the regulation of both enzymes in hypertension would explain the differences observed in the Vimang effect.

Anti-Hypertensive Effects of Acacia Polyphenol in Spontaneously Hypertensive Rats

PubMed Central

Ikarashi, Nobutomo; Toda, Takahiro; Hatakeyama, Yusuke; Kusunoki, Yoshiki; Kon, Risako; Mizukami, Nanaho; Kaneko, Miho; Ogawa, Sosuke; Sugiyama, Kiyoshi

2018-01-01

We have previously demonstrated that acacia polyphenol (AP) exerts strong anti-obesity, anti-diabetic, and anti-atopic dermatitis effects. In the present study, we investigated the anti-hypertensive effects of AP. Spontaneously hypertensive rats (SHR) with hypertension and control Wistar Kyoto rats (WKY) were used. WKY and SHR were fed AP-containing food or AP-free food (control group) ad libitum for 4 weeks, and their blood pressures were measured. After AP administration, both systolic and diastolic blood pressures were significantly lower in the SHR group than in the control group. There were no differences in the systolic or diastolic blood pressure of WKY between the AP group and the control group. Angiotensin-converting enzyme (ACE) activity, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression, and superoxide dismutase (SOD) activity in SHR kidneys were not altered by AP administration. Blood SOD activity in SHR was significantly higher in the AP group than in the control group. AP exerts anti-hypertensive effects on hypertension but has almost no effect on normal blood pressure. The anti-hypertensive effects of AP may be related to the anti-oxidative effects of increased blood SOD activity. PMID:29494506

INCREASED OXIDATIVE STRESS AND DOWN REGULATION OF ENDOTHELIAL NITRIC OXIDE SYNTHASE (ENOS) IN THE KIDNEY ATTEN- UATE THE RESPONSIVENESS OF (XlB ADRENERGIC RECEPTORS IN THE KIDNEY OF RATS WITH LEFT VENTRICULAR HYPERTROPHY.

PubMed

Ahmad, Ashfaq; Sattar, Munavvar; Khan, Safia Akhtar; Abdullah, Nor A; Johns, Edward J; Afzal, Samina

2017-03-01

Present study explored endothelial nitric oxide synthase/nitric oxide (eNOS/NO) pathway in the kidney and role of αIB adrenergic receptor in the regulation of renal vasculature in the rats with left ventricular hypertrophy (LVH). LVH was induced by administering isoprenaline 5 mg/kg (s.c. 72 h. apart) and caffeine (62 mg/L in drinking water) for 14 days. Quantification of molecular expression of eNOS in kidney was performed by quantitative Real Time Polymerase Chain Reaction (qPCR). Renal vasoconstrictor responses were measured by administering noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) in pre-drug phase, low dose and high dose phases of chloroethylelonidine (CEC), a selective of (αIB adrenergic receptor antagonist. In the kidney of LVH male Wistar Kyoto (WKY) rats eNOS was significantly down regulated (p < 0.05) by 74% relative to Control WKY (taken as 100%). The high dose 5 CEC attenuated the vasoconstrictor responses to NA by 41%, PE by 43% and ME by 33% in the LVH-WKY when compared to the same dose phase in Control WKY group. In LVH, increased oxidative stress in kidney and increased ACE activity in the plasma resulted in down regulation of eNOS/NO in the kidney. The renal vasoconstrictor responses to adrenergic agonist are blunted in LVH and (αIB adrenergic receptor is functional subtype in renal vasculature in LVH.

Omega-3 Fatty Acids Supplementation Differentially Modulates the SDF-1/CXCR-4 Cell Homing Axis in Hypertensive and Normotensive Rats.

PubMed

Halmenschlager, Luiza; Lehnen, Alexandre Machado; Marcadenti, Aline; Markoski, Melissa Medeiros

2017-08-01

We assessed the effect of acute and chronic dietary supplementation of ω-3 on lipid metabolism and cardiac regeneration, through its influence on the Stromal Derived Factor-1 (SDF-1) and its receptor (CXCR4) axis in normotensive and hypertensive rats. Male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were allocated in eight groups (of eight animals each), which received daily orogastric administration of ω-3 (1 g) for 24 h, 72 h or 2 weeks. Blood samples were collected for the analysis of the lipid profile and SDF-1 systemic levels (ELISA). At the end of the treatment period, cardiac tissue was collected for CXCR4 expression analysis (Western blot). The use of ω-3 caused a reduction in total cholesterol levels ( p = 0.044), and acutely activated the SDF-1/CXCR4 axis in normotensive animals ( p = 0.037). In the presence of the ω-3, after 72 h, SDF-1 levels decreased in WKY and increased in SHR ( p = 0.017), and tissue expression of the receptor CXCR4 was higher in WKY than in SHR ( p = 0.001). The ω-3 fatty acid supplementation differentially modulates cell homing mediators in normotensive and hypertensive animals. While WKY rats respond acutely to omega-3 supplementation, showing increased release of SDF-1 and CXCR4, SHR exhibit a weaker, delayed response.

Renal mitochondrial dysfunction in spontaneously hypertensive rats is attenuated by losartan but not by amlodipine.

PubMed

de Cavanagh, Elena M V; Toblli, Jorge E; Ferder, León; Piotrkowski, Bárbara; Stella, Inés; Inserra, Felipe

2006-06-01

Mitochondrial dysfunction is associated with cardiovascular damage; however, data on a possible association with kidney damage are scarce. Here, we aimed at investigating whether 1) kidney impairment is related to mitochondrial dysfunction; and 2) ANG II blockade, compared with Ca2+ channel blockade, can reverse potential mitochondrial changes in hypertension. Eight-week-old male spontaneously hypertensive rats (SHR) received water containing losartan (40 mg.kg-1.day-1, SHR+Los), amlodipine (3 mg.kg-1.day-1, SHR+Amlo), or no additions (SHR) for 6 mo. Wistar-Kyoto rats (WKY) were normotensive controls. Glomerular and tubulointerstitial damage, systolic blood pressure, and proteinuria were higher, and creatinine clearance was lower in SHR vs. SHR+Los and WKY. In SHR+Amlo, blood pressure was similar to WKY, kidney function was similar to SHR, and renal lesions were lower than in SHR, but higher than in SHR+Los. In kidney mitochondria from SHR and SHR+Amlo, membrane potential, nitric oxide synthase, manganese-superoxide dismutase and cytochrome oxidase activities, and uncoupling protein-2 content were lower than in SHR+Los and WKY. In SHR and SHR+Amlo, mitochondrial H2O2 production was higher than in SHR+Los and WKY. Renal glutathione content was lower in SHR+Amlo relative to SHR, SHR+Los, and WKY. In SHR and SHR+Amlo, glutathione was relatively more oxidized than in SHR+Los and WKY. Tubulointerstitial alpha-smooth muscle actin labeling was inversely related to manganese-superoxide dismutase activity and uncoupling protein-2 content. These findings suggest that oxidant stress is associated with renal mitochondrial dysfunction in SHR. The mitochondrial-antioxidant actions of losartan may be an additional or alternative way to explain some of the beneficial effects of AT1-receptor antagonists.

Role of gap junctions in the contractile response to agonists in the mesenteric artery of spontaneously hypertensive rats.

PubMed

Ma, Ke-Tao; Li, Xin-Zhi; Li, Li; Jiang, Xue-Wei; Chen, Xin-Yan; Liu, Wei-Dong; Zhao, Lei; Zhang, Zhong-Shuang; Si, Jun-Qiang

2014-02-01

To investigate the effects of hypertension on the changes in gap junctions between vascular smooth muscle cells (VSMCs) in the mesenteric artery (MA) of spontaneously hypertensive rats (SHRs). Whole-cell patch clamp, pressure myography, real-time quantitative reverse transcription PCR (qRT-PCR), western blot analysis and transmission electron microscopy were used to examine the differences in expression and function of the gap junction between MA VSMCs of SHR and control normotensive Wistar-Kyoto (WKY) rats. (1) Whole-cell patch clamp measurements showed that the membrane capacitance and conductance of in-situ MA VSMCs of SHR were significantly greater than those of WKY rats (P<0.05), suggesting enhanced gap junction coupling between MA VSMCs of SHR. (2) The administration of phenylephrine (PE) and KCl (an endothelium-independent vasoconstrictor) initiated more pronounced vasoconstriction in SHR versus WKY rats (P<0.05). Furthermore, 2-APB (a gap junction inhibitor) attenuated PE- and KCl-induced vasoconstriction, and the inhibitory effects of 2-APB were significantly greater in SHR (P<0.05). (3) The expression of connexin 45 (Cx45) mRNA and protein in the MA was greater in SHR versus WKY rats (P<0.05). The level of phosphorylated Cx43 was significantly higher in SHR versus WKY rats (P<0.05), although the expression of total Cx43 mRNA and protein in the MA was equivalent between SHR and WKY rats. Electron microscopy revealed that the gap junctions were significantly larger in SHR versus WKY rats. Increases in the expression of Cx45 and phosphorylation of Cx43 may contribute to the enhancement of communication across gap junctions between MA VSMCs of SHR, which may increase the contractile response to agonists.

Role of phosphatidylinositol 3-kinase in angiotensin II regulation of norepinephrine neuromodulation in brain neurons of the spontaneously hypertensive rat.

PubMed

Yang, H; Raizada, M K

1999-04-01

Chronic stimulation of norepinephrine (NE) neuromodulation by angiotensin II (Ang II) involves activation of the Ras-Raf-MAP kinase signal transduction pathway in Wistar Kyoto (WKY) rat brain neurons. This pathway is only partially responsible for this heightened action of Ang II in the spontaneously hypertensive rat (SHR) brain neurons. In this study, we demonstrate that the MAP kinase-independent signaling pathway in the SHR neuron involves activation of PI3-kinase and protein kinase B (PKB/Akt). Ang II stimulated PI3-kinase activity in both WKY and SHR brain neurons and was accompanied by its translocation from the cytoplasmic to the nuclear compartment. Although the magnitude of stimulation by Ang II was comparable, the stimulation was more persistent in the SHR neuron compared with the WKY rat neuron. Inhibition of PI3-kinase had no significant effect in the WKY rat neuron. However, it caused a 40-50% attenuation of the Ang II-induced increase in norepinephrine transporter (NET) and tyrosine hydroxylase (TH) mRNAs and [3H]-NE uptake in the SHR neuron. In contrast, inhibition of MAP kinase completely attenuated Ang II stimulation of NET and TH mRNA levels in the WKY rat neuron, whereas it caused only a 45% decrease in the SHR neuron. However, an additive attenuation was observed when both kinases of the SHR neurons were inhibited. Ang II also stimulated PKB/Akt activity in both WKY and SHR neurons. This stimulation was 30% higher and lasted longer in the SHR neuron compared with the WKY rat neuron. In conclusion, these observations demonstrate an exclusive involvement of PI3-kinase-PKB-dependent signaling pathway in a heightened NE neuromodulatory action of Ang II in the SHR neuron. Thus, this study offers an excellent potential for the development of new therapies for the treatment of centrally mediated hypertension.

Effect of nitro-L-arginine on electrical and mechanical responses to acetylcholine in the superior mesenteric artery from stroke-prone hypertensive rat

PubMed Central

Ghisdal, Philippe; Godfraind, Théophile; Morel, Nicole

1999-01-01

High salt diet is known to aggravate the vascular pathology in spontaneously hypertensive stroke-prone rats (SHR-SP). The aim of the present study was to assess the involvement of endothelial dysfunction in this effect. Contractile tension and membrane potential were simultaneously recorded in superior mesenteric artery rings of untreated and NaCl-loaded (1% NaCl in the drinking water) SHR-SP and normotensive Wistar Kyoto rats (WKY).In unstimulated artery, hyperpolarization evoked by acetylcholine was not different in WKY and in NaCl-loaded WKY; it was reduced in SHR-SP and further reduced in NaCl-loaded SHR-SP. Hyperpolarization was unaffected by Nω-nitro-L-arginine (L-NA) but was abolished in high-KCl solution.In noradrenaline-stimulated artery, ACh-evoked hyperpolarization and relaxation were not different in WKY and in SHR-SP. NaCl-treatment did not affect the responses to ACh in WKY but decreased maximum relaxation in SHR-SP from 93±2% to 72±7% of the contraction. In WKY, in NaCl-loaded WKY and in SHR-SP, L-NA similarly shifted the concentration-relaxation curve to ACh to the right and depressed its maximum but L-NA did not affect the hyperpolarization to ACh. In NaCl-loaded SHR-SP, L-NA blunted the effects of ACh on membrane potential and on contraction.The NO donor SNAP abolished the depolarization and the contraction evoked by noradrenaline with the same potency in WKY and in untreated SHR-SP but was more potent in NaCl-loaded SHR-SP.In KCl-contracted arteries the relaxations to ACh were not different in WKY and SHR-SP but NaCl-loaded SHR-SP were more sensitive to ACh.The results showed that NaCl-rich diet markedly reduced the L-NA-resistant responses to ACh and increased the sensitivity to NO in SHR-SP. PMID:10602331

Central cardiovascular action of urotensin II in spontaneously hypertensive rats.

PubMed

Lin, Yingzi; Tsuchihashi, Takuya; Matsumura, Kiyoshi; Fukuhara, Masayo; Ohya, Yusuke; Fujii, Koji; Iida, Mitsuo

2003-10-01

We have previously reported that urotensin II acts on the central nervous system to increase blood pressure in normotensive rats. In the present study, we have determined the central cardiovascular action of urotensin II in spontaneously hypertensive rats (SHR). Intracerebroventricular (ICV) injection of urotensin II elicited a dose-dependent increase in blood pressure in both SHR and normotensive Wistar-Kyoto rats (WKY). The changes in mean arterial pressure induced by ICV urotensin II at doses of 1 and 10 nmol in the WKY were 8 +/- 2 and 23 +/- 3 mmHg, respectively. ICV administration of urotensin II caused significantly greater increases in blood pressure in SHR (16 +/- 3 mmHg at 1 nmol and 35 +/- 3 mmHg at 10 nmol, respectively) compared with those in WKY. Urotensin II (10 nmol) elicited significant and comparable increases in heart rate in SHR (107 +/- 10 bpm) and WKY (101 +/- 21 bpm). Plasma epinephrine concentrations after ICV administration of 10 nmol urotensin II were 203 +/- 58 pmol/ml in SHR and 227 +/- 47 pmol/ml in WKY, which tended to be higher than those in artificial cerebrospinal fluid-injected rats (73+/- 7 and 87 +/- 28 pmol/ml, respectively, p < 0.1). The immunoreactivity of urotensin II receptor GPR 14 was expressed extensively in the glial cells within the brainstem, hypothalamus, and thalamus. These results suggest that central urotensin II may play a role in the pathogenesis of hypertension in SHR. Since GPR 14 was expressed in the glial cells of the brain, urotensin II may act as a neuromodulator to regulate blood pressure.

Losartan reduced connexin43 expression in left ventricular myocardium of spontaneously hypertensive rats

PubMed Central

Zhao, Li-li; Chen, Hong-juan; Chen, Jun-zhu; Yu, Min; Ni, Yun-lan; Zhang, Wei-fang

2008-01-01

Objective: To assess the effect of angiotensin II type 1 (AT1) receptor antagonist losartan on myocardium connexin43 (Cx43) gap junction (GJ) expression in spontaneously hypertensive rats (SHRs) and investigate possible mechanisms. Methods: Sixteen 9-week-old male SHRs and 8 age-matched male Wistar-Kyoto (WKY) rats were included in this study. SHRs were randomly divided into two groups to receive losartan at 30 mg/(kg·d) by oral gavage once daily for 8 weeks (SHR-L) or vehicle (0.9% saline) to act as controls (SHR-V); WKY rats receiving vehicle for 8 weeks served as normotensive controls. At the end of the experiment, rats were sacrificed and the hearts were removed. Expressions of Cx43 and nuclear factor-kappaB p65 (NF-κB p65) proteins in all three groups were observed and further investigations on the effect of angiotensin II type 1 receptor antagonist losartan (30 mg/(kg·d), 8 weeks) on Cx43 expression were conducted with Western blot and immunohistochemistry. NF-κB p65 protein in nuclear extracts was determined by Western blot. Results: Left ventricular (LV) hypertrophy was prominent in SHRs, Cx43 and NF-κB p65 protein expressions were obviously upregulated and Cx43 distribution was dispersed over the cell surface. Treatment with losarton reduced the over-expressions of Cx43 and NF-κB p65 in LV myocardium. The distribution of Cx43 gap junction also became much regular and confined to intercalated disk after losartan treatment. Conclusion: Cx43 level was upregulated in LV myocardium of SHR during early stage of hypertrophy. Angiotensin II type 1 receptor antagonist losartan prevented Cx43 gap junction remodeling in hypertrophied left ventricles, possibly through the NF-κB pathway. PMID:18543397

Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats.

PubMed

De Bruin, N M W J; Kiliaan, A J; De Wilde, M C; Broersen, L M

2003-07-01

Rationale. Hypertension is considered a risk factor for the development of cognitive disorders, because of its negative effects on cerebral vasculature and blood flow. Genetically induced hypertension in rats has been associated with a range of cognitive impairments. Therefore, spontaneously hypertensive rats (SHR) can potentially be used as a model for cognitive deficits in human subjects. Consecutively, it can be determined whether certain food components can improve cognition in these rats. Objective. The present study aimed to determine whether SHR display specific deficits in attention, learning, and memory function. Additionally, effects of chronic uridine and choline administration were studied. Methods. 5-7 months old SHR were compared with normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. (a) The operant delayed non-matching-to-position (DNMTP) test was used to study short-term memory function. (b) The five-choice serial reaction time (5-CSRT) task was used to assess selective visual attention processes. (c) Finally, the Morris water maze (MWM) acquisition was used as a measure for spatial learning and mnemonic capabilities. Results. (1) SHR exhibited significantly impaired performance in the 5-CSRT test in comparison with the two other rat strains. Both the SHR and WKY showed deficits in spatial learning when compared with the SD rats. (2) Uridine and choline supplementation normalized performance of SHR in the 5-CSRT test. (3) In addition, uridine and choline treatment improved MWM acquisition in both WKY and SHR rats. Conclusion. The present results show that the SHR have a deficiency in visual selective attention and spatial learning. Therefore, the SHR may provide an interesting model in the screening of substances with therapeutic potential for treatment of cognitive disorders. A combination of uridine and choline administration improved selective attention and spatial learning in SHR.

DIFFERENTIAL EFFECTS OF CARBARYL IN BRAIN ACONITASE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE (SHR) AND WISTAR-KYOTO (WKY) RATS.

EPA Science Inventory

Animal models of susceptibility are crucial for quantitative human health risk assessment. Spontaneously hypertensive rats (SHR) have long been used in studies on the etiology and mechanisms of hypertension and are known to be prone to oxidative stress. Previous studies indica...

Schedule-induced polydipsia in the spontaneously hypertensive rat and its relation to impulsive behaviour.

PubMed

Ibias, Javier; Pellón, Ricardo

2011-09-30

Eight Spontaneously Hypertensive Rat (SHR), 8 Wistar-Kyoto (WKY) and 8 Wistar rats, all male, maintained at 80-85% of their free-feeding weight by controlled access to food, were exposed to a series of fixed time (FT) schedules whereby food pellets were regularly delivered regardless of the animals' behaviour. The FT values used were 9, 15, 30, 60, 120 and 180 s, with the order of presentation of the schedules among the animals being counterbalanced (except under the FT 120-s and 180-s schedules, which were successively presented as the last two of the series). Due to freely available access to water, the animals developed schedule-induced drinking under all FT schedules, marked by the characteristic bitonic function that relates the number of licks and amount of water drunk to the length of the inter-food interval. Wistar and WKY rats displayed maximum drinking under an FT 15-s schedule, with WKY rats registering lower quantities across all FT values. Among SHR rats, maximum schedule-induced polydipsia was observed under the FT 30-s schedule, with a rightward shift in the bitonic function compared to controls. For long FT values, the temporal distribution of licks within inter-food intervals was shifted slightly towards the right in the SHR rats. In a subsequent study, only the SHR and Wistar rats were used, and the animals were exposed to a delay-discounting procedure. The rats were faced with successive choices, in which they could choose between an immediate reward of one food pellet and another of four food pellets at a delay of 3, 6, 12 or 24s. In the case of the longer delays, SHR rats chose the immediate reward of lower magnitude more often than did their Wistar counterparts, and also committed a greater number of omissions during the forced-choice trials of the procedure. The results indicate that differences in schedule-induced polydipsia are related to indexes of cognitive rather than motor impulsivity, a finding in line with the theoretical idea that

Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shannahan, Jonathan H.; Alzate, Oscar; Winnik, Witold M.

Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases inmore » α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins

The Effects of New Alibernet Red Wine Extract on Nitric Oxide and Reactive Oxygen Species Production in Spontaneously Hypertensive Rats

PubMed Central

Kondrashov, Alexey; Vranková, Stanislava; Dovinová, Ima; Ševčík, Rudolf; Parohová, Jana; Barta, Andrej; Pecháňová, Olga; Kovacsová, Maria

2012-01-01

We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE) and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs). Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day) for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR. PMID:22720118

Use of the Exponential and Exponentiated Demand Equations to Assess the Behavioral Economics of Negative Reinforcement

PubMed Central

Fragale, Jennifer E. C.; Beck, Kevin D.; Pang, Kevin C. H.

2017-01-01

Abnormal motivation and hedonic assessment of aversive stimuli are symptoms of anxiety and depression. Symptoms influenced by motivation and anhedonia predict treatment success or resistance. Therefore, a translational approach to the study of negatively motivated behaviors is needed. We describe a novel use of behavioral economics demand curve analysis to investigate negative reinforcement in animals that separates hedonic assessment of footshock termination (i.e., relief) from motivation to escape footshock. In outbred Sprague Dawley (SD) rats, relief increased as shock intensity increased. Likewise, motivation to escape footshock increased as shock intensity increased. To demonstrate the applicability to anxiety disorders, hedonic and motivational components of negative reinforcement were investigated in anxiety vulnerable Wistar Kyoto (WKY) rats. WKY rats demonstrated increased motivation for shock cessation with no difference in relief as compared to control SD rats, consistent with a negative bias for motivation in anxiety vulnerability. Moreover, motivation was positively correlated with relief in SD, but not in WKY. This study is the first to assess the hedonic and motivational components of negative reinforcement using behavioral economic analysis. This procedure can be used to investigate positive and negative reinforcement in humans and animals to gain a better understanding of the importance of motivated behavior in stress-related disorders. PMID:28270744

Activation of D4 dopamine receptor decreases AT1 angiotensin II receptor expression in rat renal proximal tubule cells

PubMed Central

Chen, Ken; Deng, Kun; Wang, Xiaoyan; Wang, Zhen; Zheng, Shuo; Ren, Hongmei; He, Duofen; Han, Yu; Asico, Laureano D.; Jose, Pedro A.; Zeng, Chunyu

2014-01-01

The dopaminergic and renin angiotensin systems interact to regulate blood pressure. Disruption of the D4 dopamine receptor gene in mice produces hypertension that is associated with increased renal AT1 receptor expression. We hypothesize that the D4 receptor can inhibit AT1 receptor expression and function in renal proximal tubules (RPTs) cells from Wistar-Kyoto (WKY) rats but the D4 receptor regulation of AT1 receptor is aberrant in RPT cells from spontaneously hypertensive rats (SHRs). The D4 receptor agonist, PD168077, decreased AT1 receptor protein expression in a time and concentration-dependent manner in WKY cells. By contrast, in SHR cells, PD168077 increased AT1 receptor protein expression. The inhibitory effect of D4 receptor on AT1 receptor expression in WKY cells was blocked by a calcium channel blocker, nicardipine, or calcium-free medium, indicating that calcium is involved in the D4 receptor-mediated signaling pathway. Angiotensin II increased Na+-K+ ATPase activity in WKY cells. Pretreatment with PD168077 decreased the stimulatory effect of angiotensin II on Na+-K+ ATPase activity in WKY cells. In SHR cells, the inhibitory effect of D4 receptor on angiotensin II-mediated stimulation of Na+-K+ ATPase activity was aberrant; pretreatment with PD168077 augmented the stimulatory effect of AT1 receptor on Na+-K+ ATPase activity in SHR cells. This was confirmed in vivo; pre-treatment with PD128077 for one week augmented the anti-hypertensive and natriuretic effect of losartan in SHRs but not in WKY rats. We suggest that an aberrant interaction between D4 and AT1 receptors may play a role in the abnormal regulation of sodium excretion in hypertension. PMID:25368031

Magnolol Administration in Normotensive Young Spontaneously Hypertensive Rats Postpones the Development of Hypertension: Role of Increased PPAR Gamma, Reduced TRB3 and Resultant Alleviative Vascular Insulin Resistance

PubMed Central

Fu, Feng; Zhang, Wei; Su, Feifei; Liu, Fange; Ji, Lele; Gao, Feng; Su, Hui; Sun, Xin; Zhang, Haifeng

2015-01-01

Patients with prehypertension are more likely to progress to manifest hypertension than those with optimal or normal blood pressure. However, the mechanisms underlying the development from prehypertension to hypertension still remain largely elusive and the drugs for antihypertensive treatment in prehypertension are absent. Here we determined the effects of magnolol (MAG) on blood pressure and aortic vasodilatation to insulin, and investigated the underlying mechanisms. Four-week-old male spontaneous hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) control rats were used. Our results shown that treatment of young SHRs with MAG (100 mg/kg/day, o.g.) for 3 weeks decreased blood pressure, improved insulin-induced aorta vasodilation, restored Akt and eNOS activation stimulated by insulin, and increased PPARγ and decreased TRB3 expressions. In cultured human umbilical vein endothelial cells (HUVECs), MAG incubation increased PPARγ, decreased TRB3 expressions, and restored insulin-induced phosphorylated Akt and eNOS levels and NO production, which was blocked by both PPARγ antagonist and siRNA targeting PPARγ. Improved insulin signaling in HUVECs by MAG was abolished by upregulating TRB3 expression. In conclusion, treatment of young SHRs with MAG beginning at the prehypertensive stage decreases blood pressure via improving vascular insulin resistance that is at least partly attributable to upregulated PPARγ, downregulated TRB3 and consequently increased Akt and eNOS activations in blood vessels in SHRs. PMID:25793876

Decreased expression of Na+-H+ exchanger isoforms 1 and 3 in denervated spontaneously hypertensive rat kidney.

PubMed

Li, Jianling; He, Qiaoling; Li, Qingjie; Huang, Rongjie; Wei, Xiaoyan; Pan, Xiaofeng; Wu, Weifeng

2018-05-22

To determine whether the sympathetic nerve plays a role in the regulation of Na + -H + exchange (NHE) in the kidney of spontaneously hypertensive rats (SHR), we investigated the expression of NHE and NHE regulatory protein family (NHERF) in the denervated kidneys compared with intact kidneys. Twelve-week-old male SHR and age-matched Wistar Kyoto (WKY) rats were used. SHR were randomly assigned to the renal denervated (RDNX, n = 8) or Sham (n = 8) groups. The protein and mRNA expression of NHE1, NHE3, NHERF1 and NHERF2 were assessed in the kidney of the groups. Following the renal denervation, immunohistochemistry and western blot analysis showed that NHE1 and NHE3 protein were significantly decreased in the kidney compared with Sham group. NHERF1 protein expression was significantly increased in RDNX compared with Sham group, whereas NHERF2 protein expression was significantly decreased after renal denervation. Similar results were observed at the mRNA level of NHE1, NHE3, NHERF1 and NHERF2 expression. The present findings suggest that the renal sympathetic nervous system plays a role in the regulation of NHE1 and NHE3 in the kidney of SHR, and NHERF1 may be involved in the expression of NHE3 in the kidney of SHR.

Blockade of α2-adrenergic receptors in prelimbic cortex: impact on cocaine self-administration in adult spontaneously hypertensive rats following adolescent atomoxetine treatment.

PubMed

Baskin, Britahny M; Nic Dhonnchadha, Bríd Á; Dwoskin, Linda P; Kantak, Kathleen M

2017-10-01

Research with the spontaneously hypertensive rat (SHR) model of attention deficit/hyperactivity disorder demonstrated that chronic methylphenidate treatment during adolescence increased cocaine self-administration established during adulthood under a progressive ratio (PR) schedule. Compared to vehicle, chronic atomoxetine treatment during adolescence failed to increase cocaine self-administration under a PR schedule in adult SHR. We determined if enhanced noradrenergic transmission at α2-adrenergic receptors within prefrontal cortex contributes to this neutral effect of adolescent atomoxetine treatment in adult SHR. Following treatment from postnatal days 28-55 with atomoxetine (0.3 mg/kg) or vehicle, adult male SHR and control rats from Wistar-Kyoto (WKY) and Wistar (WIS) strains were trained to self-administer 0.3 mg/kg cocaine. Self-administration performance was evaluated under a PR schedule of cocaine delivery following infusion of the α2-adrenergic receptor antagonist idazoxan (0 and 10-56 μg/side) directly into prelimbic cortex. Adult SHR attained higher PR break points and had greater numbers of active lever responses and infusions than WKY and WIS. Idazoxan dose-dependently increased PR break points and active lever responses in SHR following adolescent atomoxetine vs. vehicle treatment. Behavioral changes were negligible after idazoxan pretreatment in SHR following adolescent vehicle or in WKY and WIS following adolescent atomoxetine or vehicle. α2-Adrenergic receptor blockade in prelimbic cortex of SHR masked the expected neutral effect of adolescent atomoxetine on adult cocaine self-administration behavior. Moreover, greater efficacy of acute idazoxan challenge in adult SHR after adolescent atomoxetine relative to vehicle is consistent with the idea that chronic atomoxetine may downregulate presynaptic α2A-adrenergic autoreceptors in SHR.

A combined effect of dextromethorphan and melatonin on neuropathic pain behavior in rats.

PubMed

Wang, Shuxing; Zhang, Lin; Lim, Grewo; Sung, Backil; Tian, Yinghong; Chou, Chiu-Wen; Hernstadt, Hayley; Rusanescu, Gabriel; Ma, Yuxin; Mao, Jianren

2009-09-08

Previous study has shown that administration of melatonin into the anterior cingulate cortex contralateral to peripheral nerve injury prevented exacerbation of mechanical allodynia with a concurrent improvement of depression-like behavior in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats. In the present study, we examined the effect of the individual versus combined treatment of melatonin and/or dextromethorphan (DM), a clinically available N-methyl-d-aspartate (NMDA) receptor antagonist, on pain behaviors in WKY rats with chronic constriction sciatic nerve injury (CCI). Pain behaviors (thermal hyperalgesia and mechanical allodynia) were established at one week after CCI. WKY rats were then treated intraperitoneally with various doses of melatonin, DM or their combination once daily for the following week. At the end of this one-week treatment, behavioral tests were repeated in these same rats. While DM alone was effective in reducing thermal hyperalgesia at three tested doses (15, 30 or 60 mg/kg), it reduced mechanical allodynia only at high doses (30 or 60 mg/kg). By comparison, administration of melatonin alone was effective in reducing thermal hyperalgesia only at the highest dose (120 mg/kg, but not 30 or 60 mg/kg) tested in this experiment. Melatonin alone failed to reverse allodynia at all three tested doses (30, 60 and 120 mg/kg). However, the combined intraperitoneal administration of melatonin (30 mg/kg) and DM (15 mg/kg) effectively reversed both thermal hyperalgesia and mechanical allodynia although each individual dose alone did not reduce pain behaviors. These results suggest that a combination of melatonin with a clinically available NMDA receptor antagonist might be more effective than either drug alone for the treatment of neuropathic pain.

The effects of running exercise on oxidative capacity and PGC-1α mRNA levels in the soleus muscle of rats with metabolic syndrome.

PubMed

Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Kouzaki, Motoki; Gu, Ning; Takeda, Isao; Tsuda, Kinsuke; Ishihara, Akihiko

2012-03-01

Skeletal muscles in animals with metabolic syndrome exhibit reduced oxidative capacity. We investigated the effects of running exercise on fiber characteristics, oxidative capacity, and mRNA levels in the soleus muscles of rats with metabolic syndrome [SHR/NDmcr-cp (cp/cp); CP]. We divided 5-week-old CP rats into non-exercise (CP) and exercise (CP-Ex) groups. Wistar-Kyoto rats (WKY) were used as the control group. CP-Ex rats were permitted voluntary exercise on running wheels for 10 weeks. Triglyceride levels were higher and adiponectin levels lower in the CP and CP-Ex groups than in the WKY group. However, triglyceride levels were lower and adiponectin levels higher in the CP-Ex group than in the CP group. The soleus muscles in CP-Ex rats contained only high-oxidative type I fibers, whereas those in WKY and CP rats contained type I, IIA, and IIC fibers. Muscle succinate dehydrogenase (SDH) activity was higher in the CP-Ex group than in the CP group; there was no difference in SDH activity between the WKY and CP-Ex groups. Muscle proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA levels were higher in the CP-Ex group than in the CP group; there was no difference in PGC-1α mRNA levels between the WKY and CP-Ex groups. In CP-Ex rats, longer running distance was associated with increased muscle SDH activity and PGC-1α mRNA levels. We concluded that running exercise restored decreased muscle oxidative capacity and PGC-1α mRNA levels and improved hypertriglyceridemia in rats with metabolic syndrome.

Left ventricular hypertrophy does not prevent heart failure in experimental hypertension.

PubMed

Hernán Gómez Llambí, H; Cao, G; Donato, M; Suárez, D; Ottaviano, G; Müller, A; Buchholz, B; Gelpi, R; Otero-Losada, M; Milei, J

2017-07-01

Left ventricular hypertrophy (LVH) secondary to hypertension has been accepted to prevent heart failure (HF) while paradoxically increasing cardiovascular morbi-mortality. To evaluate whether antihypertensive treatment inhibits LVH, restores beta-adrenergic response and affects myocardial oxidative metabolism. Ninety spontaneously hypertensive rats (SHR) were distributed into groups and treated (mg/kg, p.o.) with: losartan 30 (L), hydralazine 11 (H), rosuvastatin 10 (R), carvedilol 20 (C). Hypertension control group comprised 18 normotensive rats (Wistar-Kyoto, WKY). Following euthanasia at 16months, contractility was measured in 50% of rats (Langendorff system) before and after isoproterenol (Iso) 10 -9 M, 10 -7 M and 10 -5 M stimulation. Left ventricular weight (LVW) was measured in the remaining hearts, and normalized by BW. Expression of thioredoxin 1 (Trx-1), peroxyredoxin 2 (Prx-2), glutaredoxin 3 (Grx-3), caspase-3 and brain natriuretic peptide (BNP) was determined. Systolic blood pressure (mmHg): 154±3 (L), 137±1 (H), 190±3 (R)*, 206±3 (SHR)*, 183±1 (C)**, and 141±1 (WKY) (*p<0.05 vs. L, H, WKY, **p<0.05 vs. L, H, WKY, SHR). LVW/BW was higher in SHR and R (p<0.05). Groups SHR, R and C evidenced baseline contractile depression. Response to Iso 10 -5 M was similar in WKY and L. Expression of Trx-1, Prx-2 and Grx-3 increased in C, H, R and L (p<0.01). Present findings argue against the traditional idea and support that LVH might not be required to prevent HF. Increased expression of thioredoxins by antihypertensive treatment might be involved in protection from HF. Copyright © 2017 Elsevier B.V. All rights reserved.

CARDIOVASCULAR RESPONSES IN UNRESTRAINED WKY-RATS TO INHALED ULTRAFINE CARBON PARTICLES

EPA Science Inventory

Abstract
This study provides evidence for adverse cardiac effects of inhaled ultrafine particles (UFPs) in healthy WKY rats. Short term exposure (24 h) with carbon UFPs (180 ?g?m ?) induced a moderate but significant heart rate increase of 18 bpm (4.8 %) in association with a ...

Sex differences in depressive, anxious behaviors and hippocampal transcript levels in a genetic rat model.

PubMed

Mehta, N S; Wang, L; Redei, E E

2013-10-01

Major depressive disorder (MDD) is a common, debilitating illness with high prevalence of comorbid anxiety. The incidence of depression and of comorbid anxiety is much higher in women than in men. These gender biases appear after puberty and their etiology is mostly unknown. Selective breeding of the Wistar Kyoto (WKY) rat strain, an accepted model of adult and adolescent depression, resulted in two fully inbred substrains. Adult WKY more immobile (WMI) rats of both sexes consistently show increased depression-like behavior in the forced swim test when compared with the control WKY less immobile (WLI) strain. In contrast, here we show that while adult female WMIs and WLIs both display high anxiety-like behaviors, only WLI males, but not WMI males, show this behavior. Moreover, the behavioral profile of WMI males is consistent from early adolescence to adulthood, but the high depression- and anxiety-like behaviors of the female WMIs appear only in adulthood. These sex-specific behavioral patterns are paralleled by marked sex differences in hippocampal gene expression differences established by genome-wide transcriptional analyses of 13th generation WMIs and WLIs. Moreover, sex- and age-specific differences in transcript levels of selected genes are present in the hippocampus of the current, fully inbred WMIs and WLIs. Thus, the contribution of specific genes and/or the influence of the gonadal hormonal environment to depression- and anxiety-like behaviors may differ between male and female WMIs, resulting in their distinct behavioral and transcriptomic profiles despite shared sequences of the somatic chromosomes. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

MAP kinase-independent signaling in angiotensin II regulation of neuromodulation in SHR neurons.

PubMed

Yang, H; Raizada, M K

1998-09-01

Angiotensin II (Ang II), via its interaction with the angiotensin type 1 (AT1) receptor subtype, causes enhanced stimulation of norepinephrine (NE) neuromodulation. This involves increased transcription of NE transporter, tyrosine hydroxylase, and dopamine ss-hydroxylase genes in Wistar-Kyoto rat (WKY) brain neurons. AT1 receptor-mediated regulation of certain signaling events (such as activation of the Ras-Raf-1-mitogen activated protein (MAP) kinase signaling pathway, nuclear translocation of transcription factors such as Fos and Jun, and the interactions of these factors with AP-1 binding sites) is involved in this NE neuromodulation (Lu et al. J Cell Biol. 1996;135:1609-1617). The aim of this study was to compare the signal transduction mechanism of Ang II regulation of NE neuromodulation in WKY and spontaneously hypertensive rat (SHR) brain neurons, in view of the fact that AT1 receptor expression and Ang II stimulation of NE neuromodulation are higher in SHR neurons compared with WKY neurons. Despite this hyperactivity, Ang II stimulation of Ras, Raf-1, and MAP kinase activities was comparable between the neurons from WKY and SHR. Similarly, central injections of Ang II caused a comparable stimulation of MAP kinase in the hypothalamic and brain stem areas of adult WKY and SHR. Inhibition of MAP kinase by either an MAP kinase kinase inhibitor (PD98059) or an MAP kinase antisense oligonucleotide completely attenuated the stimulatory effects of Ang II on [3H]-NE uptake, NE transporter mRNA, and tyrosine hydroxylase mRNA levels in WKY neurons. These treatments resulted in only 43% to 50% inhibition of [3H]-NE uptake and NE transporter and tyrosine hydroxylase mRNAs in SHR neurons. Thus, Ang II stimulation of NE neuromodulation was completely blocked by MAP kinase inhibition in WKY neurons and only partially blocked in the SHR neurons. These observations suggest the presence of an additional signal transduction pathway involved in NE neuromodulation in SHR neurons

DIFFERENCES IN CARDIOVASCULAR RESPONSE TO PM EXPOSURE BETWEEN SPONTANEOUSLY HYPERTENSIVE STROKE-PRONE (SHSP) AND WISTAR-KYOTO (WKY) RATS.

EPA Science Inventory

ABSTRACT BODY: Epidemiological studies have shown that cardiovascular morbidity and mortality are associated with exposure to elevated levels of ambient particulate matter (PM), notably in people with pre-existing cardiopulmonary disease. To better understand the mechanisms of PM...

REPEATED TREATMENTS WITH DOXORUBICIN CAUSES ELECTROCARDIOGRAM (ECG) CHANGES AND INCREASED VENTRICULAR PREMATURE BEATS IN WISTAR-KYOTO (WKY) RATS

EPA Science Inventory

Doxorubicin (DOX) is a widely used anthracycline anti-neoplastic drug used to treat tumors. However it has been implicated in irreversible cardiac toxicity via the generation of a proxidant semiquinone free radical, which often results in cardiomyopathy and changes in the ECG. Ac...

Tension cost correlates with mechanical and biochemical parameters in different myocardial contractility conditions

PubMed Central

Moreira, Cleci M.; Meira, Eduardo F.; Vestena, Luis; Stefanon, Ivanita; Vassallo, Dalton V.; Padilha, Alessandra S.

2012-01-01

OBJECTIVES: Tension cost, the ratio of myosin ATPase activity to tension, reflects the economy of tension development in the myocardium. To evaluate the mechanical advantage represented by the tension cost, we studied papillary muscle contractility and the activity of myosin ATPase in the left ventricles in normal and pathophysiological conditions. METHODS: Experimental protocols were performed using rat left ventricles from: (1) streptozotocin-induced diabetic and control Wistar rats; (2) N-nitro-L-arginine methyl ester (L-NAME) hypertensive and untreated Wistar rats; (3) deoxycorticosterone acetate (DOCA) salt-treated, nephrectomized and salt- and DOCA-treated rats; (4) spontaneous hypertensive rats (SHR) and Wistar Kyoto (WKY) rats; (5) rats with myocardial infarction and sham-operated rats. The isometric force, tetanic tension, and the activity of myosin ATPase were measured. RESULTS: The results obtained from infarcted, diabetic, and deoxycorticosterone acetate-salt-treated rats showed reductions in twitch and tetanic tension compared to the control and sham-operated groups. Twitch and tetanic tension increased in the N-nitro-L-arginine methyl ester-treated rats compared with the Wistar rats. Myosin ATPase activity was depressed in the infarcted, diabetic, and deoxycorticosterone acetate salt-treated rats compared with control and sham-operated rats and was increased in N-nitro-L-arginine methyl ester-treated rats. These parameters did not differ between SHR and WKY rats. In the studied conditions (e.g., post-myocardial infarction, deoxycorticosterone acetate salt-induced hypertension, chronic N-nitro-L-arginine methyl ester treatment, and streptozotocin-induced diabetes), a positive correlation between force or plateau tetanic tension and myosin ATPase activity was observed. CONCLUSION: Our results suggest that the myocardium adapts to force generation by increasing or reducing the tension cost to maintain myocardial contractility with a better mechanical

Increasing use of yellow colors in Kyoto

NASA Astrophysics Data System (ADS)

Akita, Munehira; Nara, Iwao

2002-06-01

Colors used for commercial signboards, displayed outdoors as well as indoors through windows, such as a store sign, an advertising sign, a sky sign, a poster, a placard, and a billboard were extensively surveyed in Kyoto City, Japan, in 1998. The survey showed that various kinds of yellow painted signs have increased rapidly and invaded a center area and suburbs of the city. Vivid yellow, what we called it the Y98 virus, is specially considered a color unpleasantly matched to the city image of Kyoto which was the capital of Japan for nearly 1000 years (794 to 1868) and is endowed with cultural and historic heritage. Discussions trying to find out what we could do to prevent the rapid spread of a big commercial display painted with vivid yellows what we called 'the Y98 virus' over the city will be summarized in a main text.

The Coexistence of Hypertension and Ovariectomy Additively Increases Cardiac Apoptosis.

PubMed

Lin, Yi-Yuan; Cheng, Yu-Jung; Hu, Jun; Chu, Li-Xi; Shyu, Woei-Cherng; Kao, Chung-Lan; Lin, Tzer-Bin; Kuo, Chia-Hua; Yang, Ai-Lun; Lee, Shin-Da

2016-12-06

To investigate whether the coexistence of hypertension and ovariectomy will increase cardiac Fas receptor and mitochondrial-dependent apoptotic pathways, histopathological analysis, the TUNEL assay and Western blotting were performed on the excised hearts from three groups of female spontaneously hypertensive rats (SHR), which were divided into a sham-operated group (SHR-Sham), bilaterally ovariectomized group (SHR-OVX) and normotensive Wistar Kyoto rats (WKY). Compared with the WKY group, the SHR-Sham group exhibited decreased protein levels of ERα, ERβ, p-Akt/Akt, Bcl-2, Bcl-xL and p-Bad and decreased further in the SHR-OVX group, as well as protein levels of t-Bid, Bak, Bad, Bax, cytochrome c , activated caspase-9 and activated caspase-3 (mitochondria-dependent apoptosis) increased in the SHR-Sham group and increased further in the SHR-OVX group. Compared with the WKY group, protein levels of Fas ligand, TNF-α, Fas death receptors, TNFR1, FADD and activated caspase-8 (Fas receptor-dependent apoptosis) increased in the SHR-Sham group, but did not increase in the SHR-OVX group, except Fas ligand and TNF-α. The coexistence of hypertension and ovariectomy attenuated the estrogen receptor survival pathway and appeared to additively increase the cardiac mitochondria-dependent, but not the Fas receptor-dependent apoptosis pathway, which might provide one possible mechanism for the development of cardiac abnormalities in hypertensive postmenopausal women.

Lower Squalene Epoxidase and Higher Scavenger Receptor Class B Type 1 Protein Levels Are Involved in Reduced Serum Cholesterol Levels in Stroke-Prone Spontaneously Hypertensive Rats.

PubMed

Michihara, Akihiro; Mido, Mayuko; Matsuoka, Hiroshi; Mizutani, Yurika

2015-01-01

A lower serum cholesterol level was recently shown to be one of the causes of stroke in an epidemiological study. Spontaneously hypertensive rats stroke-prone (SHRSP) have lower serum cholesterol levels than normotensive Wistar-Kyoto rats (WKY). To elucidate the mechanisms responsible for the lower serum cholesterol levels in SHRSP, we determined whether the amounts of cholesterol biosynthetic enzymes or the receptor and transporter involved in cholesterol uptake and efflux in the liver were altered in SHRSP. When the mRNA levels of seven cholesterol biosynthetic enzymes were measured using real-time polymerase chain reaction (PCR), farnesyl pyrophosphate synthase and squalene epoxidase (SQE) levels in the liver of SHRSP were significantly lower than those in WKY. SQE protein levels were significantly reduced in tissues other than the brain of SHRSP. No significant differences were observed in low-density lipoprotein (LDL) receptor (uptake of serum LDL-cholesterol) or ATP-binding cassette transporter A1 (efflux of cholesterol from the liver/formation of high-density lipoprotein (HDL)) protein levels in the liver and testis between SHRSP and WKY, whereas scavenger receptor class B type 1 (SRB1: uptake of serum HDL-cholesterol) protein levels were higher in the livers of SHRSP. These results indicated that the lower protein levels of SQE and higher protein levels of SRB1 in the liver were involved in the reduced serum cholesterol levels in SHRSP.

MicroRNA network changes in the brain stem underlie the development of hypertension.

PubMed

DeCicco, Danielle; Zhu, Haisun; Brureau, Anthony; Schwaber, James S; Vadigepalli, Rajanikanth

2015-09-01

Hypertension is a major chronic disease whose molecular mechanisms remain poorly understood. We compared neuroanatomical patterns of microRNAs in the brain stem of the spontaneous hypertensive rat (SHR) to the Wistar Kyoto rat (WKY, control). We quantified 419 well-annotated microRNAs in the nucleus of the solitary tract (NTS) and rostral ventrolateral medulla (RVLM), from SHR and WKY rats, during three main stages of hypertension development. Changes in microRNA expression were stage- and region-dependent, with a majority of SHR vs. WKY differential expression occurring at the hypertension onset stage in NTS versus at the prehypertension stage in RVLM. Our analysis identified 24 microRNAs showing time-dependent differential expression in SHR compared with WKY in at least one brain region. We predicted potential gene regulatory targets corresponding to catecholaminergic processes, neuroinflammation, and neuromodulation using the miRWALK and RNA22 databases, and we tested those bioinformatics predictions using high-throughput quantitative PCR to evaluate correlations of differential expression between the microRNAs and their predicted gene targets. We found a novel regulatory network motif consisting of microRNAs likely downregulating a negative regulator of prohypertensive processes such as angiotensin II signaling and leukotriene-based inflammation. Our results provide new evidence on the dynamics of microRNA expression in the development of hypertension and predictions of microRNA-mediated regulatory networks playing a region-dependent role in potentially altering brain-stem cardiovascular control circuit function leading to the development of hypertension. Copyright © 2015 the American Physiological Society.

Different effect of losartan and amlodipine on penile structures in male spontaneously hypertensive rats.

PubMed

Toblli, Jorge Eduardo; Stella, Inés; Mazza, Osvaldo Néstor; Ferder, León; Inserra, Felipe

2004-01-01

Erectile dysfunction is highly prevalent in hypertensive patients. Since both angiotensin II receptor type-1 blockers (ARBs) and calcium antagonists are current and effective antihypertensive drugs, the aim of this study was to determine possible differences between ARBs and calcium antagonists concerning the protection of penile structures from the deleterious effects of arterial hypertension. During 6 months, 3 groups of male spontaneously hypertensive rats (SHR) and 1 of Wistar-Kyoto (WKY) rats, as a control group, were studied: SHR without treatment; SHR with losartan (L) 30 mg/kg/day; SHR with amlodipine (A) 3 mg/kg/day, and WKY without treatment. Cavernous smooth muscle (CSM) and vascular smooth muscle (VSM) from cavernous arteries, cavernous tissue fibrosis and collagen type III (COL III) were evaluated. After 6 months, SHR+L and SHR+A showed a similar reduction in blood pressure compared with untreated SHR. However, only SHR+L and control WKY presented significantly lower values of: CSM (p < 0.01), VSM (p < 0.01), and COL III (p < 0.01) when compared with either untreated SHR or SHR+A. There was also a positive correlation between left ventricular mass and proteinuria with VSM from cavernous arteries, CSM and COL III in untreated SHR and SHR+A. These relations were not present in SHR+L and WKY. Although losartan and amlodipine achieved similar blood pressure control, losartan but not amlodipine showed a significant protective role against structural changes in the vessels and cavernous spaces of the erectile tissue caused by arterial hypertension. Copyright 2004 S. Karger AG, Basel

Noninvasive assessment of vascular structure and function in conscious rats based on in vivo imaging of the albino iris

PubMed Central

Rarick, Kevin R.; Leick, Katie M.; Burkle, Jason W.; Rotella, Diane L.; Anderson, Michael G.

2011-01-01

Experimental techniques allowing longitudinal studies of vascular disease progression or treatment effects are not readily available for most animal models. Thus, most existing studies are destined to either study individual time points or use large cohorts of animals. Here we describe a noninvasive technique for studying vascular disease that is based on in vivo imaging of the long posterior ciliary artery (LPCA) in the iris of albino rats. Using a slit-lamp biomicroscope, images of the LPCA were taken weekly in conscious normotensive Wistar Kyoto rats (WKY, n = 10) and spontaneously hypertensive rats (SHR, n = 10) for 10 wk. Using imaging software, we found that lumen diameter was significantly smaller and the wall-to-lumen (W/L) ratio larger in SHR than in WKY. Wall thickness was not different. Blood pressure correlated with the W/L ratio. Histology of the abdominal aorta also revealed a smaller lumen diameter and greater W/L ratio in SHR compared with WKY. Corneal application of the muscarinic receptor agonist pilocarpine elicited a dose-dependent vasodilation of the LPCA that could be antagonized by inhibition of nitric oxide synthase, suggesting that the pilocarpine response is mainly mediated by endothelium-derived nitric oxide. Consistent with endothelial dysfunction in SHR, pilocarpine-induced vasodilation was greater in WKY rats than in SHR. These findings indicate that in vivo imaging of the LPCA allows assessment of several structural and functional vascular parameters in conscious rats and that the LPCA responds to disease insults and pharmacologic treatments in a fashion that will make it a useful model for further studies. PMID:21389331

Diabetic Retinal Neurodegeneration Is Associated With Mitochondrial Oxidative Stress and Is Improved by an Angiotensin Receptor Blocker in a Model Combining Hypertension and Diabetes

PubMed Central

Silva, Kamila C.; Rosales, Mariana A.B.; Biswas, Subrata K.; Lopes de Faria, Jose B.; Lopes de Faria, Jacqueline M.

2009-01-01

OBJECTIVE Diabetic retinopathy displays the features of a neurodegenerative disease. Oxidative stress is involved in the pathogenesis of diabetic retinopathy. This investigation sought to determine whether hypertension exacerbates the oxidative stress, neurodegeneration, and mitochondrial dysfunction that exists in diabetic retinopathy and whether these changes could be minimized by the angiotensin II type 1 (AT1) receptor blocker (ARB) losartan. RESEARCH DESIGN AND METHODS Diabetes was induced in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. The diabetic SHRs were assigned to receive or not receive losartan. RESULTS The level of apoptosis in the retina was higher in diabetic WKY rats than in the control group, and higher levels were found in diabetic SHRs. The apoptotic cells expressed neural and glial markers. The retinal glial reaction was more evident in diabetic WKY rats and was markedly accentuated in diabetic SHRs. Superoxide production in retinal tissue increased in diabetic WKY rats, and a greater increase occurred in diabetic SHRs. Glutathione levels decreased only in diabetic SHRs. As a consequence, the levels of nitrotyrosine and 8-hydroxy 2′-deoxyguanosine, markers of oxidative stress, were elevated in diabetic groups, mainly in diabetic SHRs. Mitochondrial integrity was dramatically affected in the diabetic groups. The ARB treatment reestablished all of the above-mentioned parameters. CONCLUSIONS These findings suggest that concomitance of hypertension and diabetes exacerbates oxidative stress, neurodegeneration, and mitochondrial dysfunction in the retinal cells. These data provide the first evidence of AT1blockage as a neuroprotective treatment of diabetic retinopathy by reestablishing oxidative redox and the mitochondrial function. PMID:19289456

Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sung, Jin Young; Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr

Highlights: {yields} Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. {yields} Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. {yields} Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. {yields} Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. {yields} Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effectsmore » via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.« less

A COMBINED EFFECT OF DEXTROMETHORPHAN AND MELATONIN ON NEUROPATHIC PAIN BEHAVIOR IN RATS

PubMed Central

Wang, Shuxing; Zhang, Lin; Lim, Grewo; Sung, Backil; Tian, Yinghong; Chou, Chiu-Wen; Hernstadt, Hayley; Rusanescu, Gabriel; Ma, Yuxin; Mao, Jianren

2009-01-01

Previous study has shown that administration of melatonin into the anterior cingulate cortex contralateral to peripheral nerve injury prevented exacerbation of mechanical allodynia with a concurrent improvement of depression-like behavior in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats. In the present study, we examined the effect of the individual versus combined treatment of melatonin and/or dextromethorphan (DM), a clinically available N-methyl-D-aspartate (NMDA) receptor antagonist, on pain behaviors in WKY rats with chronic constriction sciatic nerve injury (CCI). Pain behaviors (thermal hyperalgesia and mechanical allodynia) were established at one week after CCI. WKY rats were then treated intraperitoneally with various doses of melatonin, DM or their combination once daily for the following week. At the end of this one-week treatment, behavioral tests were repeated in these same rats. While DM alone was effective in reducing thermal hyperalgesia at three tested doses (15, 30 or 60 mg/kg), it reduced mechanical allodynia only at high doses (30 or 60 mg/kg). By comparison, administration of melatonin alone was effective in reducing thermal hyperalgesia only at the highest dose (120 mg/kg, but not 30 or 60 mg/kg) tested in this experiment. Melatonin alone failed to reverse allodynia at all three tested doses (30, 60 and 120 mg/kg). However, the combined intraperitoneal administration of melatonin (30 mg/kg) and DM (15 mg/kg) effectively reversed both thermal hyperalgesia and mechanical allodynia although each individual dose alone did not reduce pain behaviors. These results suggest that a combination of melatonin with a clinically available NMDA receptor antagonist might be more effective than either drug alone for the treatment of neuropathic pain. PMID:19595681

Increased PI3-kinase in presympathetic brain areas of the spontaneously hypertensive rat.

PubMed

Veerasingham, Shereeni J; Yamazato, Masanobu; Berecek, Kathleen H; Wyss, J Michael; Raizada, Mohan K

2005-02-18

Existing evidence led us to hypothesize that increases in p85alpha, a regulatory subunit of PI3-kinase, in presympathetic brain areas contribute to hypertension. PI3-kinase p85alpha, p110alpha, and p110delta mRNA was 1.5- to 2-fold higher in the paraventricular nucleus (PVN) of spontaneously hypertensive rats (SHR) compared with their controls, Wistar Kyoto rats (WKY). The increase in p85alpha/p110delta was attenuated in SHR treated with captopril, an angiotensin (Ang)-converting enzyme inhibitor, from in utero to 6 months of age. In the rostral ventrolateral medulla (RVLM), p110delta mRNA was approximately 2-fold higher in SHR than in WKY. Moreover, the increases in mRNA were associated with higher PI3-kinase activity in both nuclei. The functional relevance was studied in neuronal cultures because SHR neurons reflect the augmented p85alpha mRNA and PI3-kinase activity. Expression of a p85 dominant-negative mutant decreased norepinephrine (NE) transporter mRNA and [3H]NE uptake by approximately 60% selectively in SHR neurons. In summary, increased p85alpha/p110delta expression in the PVN and RVLM is associated with increased PI3-kinase activity in the SHR. Furthermore, normalized PI3-kinase p85alpha/p110delta expression within the PVN might contribute to the overall effect of captopril, perhaps attributable to a consequent decrease in NE availability.

Lithium evokes a more pronounced natriuresis when administered orally than when given intravenously to salt-depleted rats.

PubMed

Mu, J; Johansson, M; Hansson, G C; Lundgren, O

1999-07-01

The effects on renal sodium excretion of giving lithium chloride (LiCl; 0.75 mmol per kg body mass) by gavage or intravenously were investigated. The experiments were carried out on Wistar-Kyoto (WKY) or spontaneously hypertensive (SHR) rats in metabolic cages. The rats had been on a low-salt diet for 4 days. Urine excretion of water, sodium and potassium was followed before and for 24 h after giving LiCl. An oral dose of LiCl evoked a more pronounced renal sodium excretion in either strain of rat as compared to that following intravenous administration, in agreement with previous observations of the effects of giving sodium chloride. Choline chloride (1.5 mmol per kg body mass) given by gavage to WKY rats or SHR evoked no change in the renal excretion of sodium. Based on the results of the present study and on observations reported in the literature, we propose that the intestinal tract contains a sodium "sensor", which upon activation releases a natriuretic factor to cause renal sodium excretion. The present results indicate that the proposed "sensor" is sensitive to lithium but not chloride ions.

Absence of “Warm-Up” during Active Avoidance Learning in a Rat Model of Anxiety Vulnerability: Insights from Computational Modeling

PubMed Central

Myers, Catherine E.; Smith, Ian M.; Servatius, Richard J.; Beck, Kevin D.

2014-01-01

Avoidance behaviors, in which a learned response causes omission of an upcoming punisher, are a core feature of many psychiatric disorders. While reinforcement learning (RL) models have been widely used to study the development of appetitive behaviors, less attention has been paid to avoidance. Here, we present a RL model of lever-press avoidance learning in Sprague-Dawley (SD) rats and in the inbred Wistar Kyoto (WKY) rat, which has been proposed as a model of anxiety vulnerability. We focus on “warm-up,” transiently decreased avoidance responding at the start of a testing session, which is shown by SD but not WKY rats. We first show that a RL model can correctly simulate key aspects of acquisition, extinction, and warm-up in SD rats; we then show that WKY behavior can be simulated by altering three model parameters, which respectively govern the tendency to explore new behaviors vs. exploit previously reinforced ones, the tendency to repeat previous behaviors regardless of reinforcement, and the learning rate for predicting future outcomes. This suggests that several, dissociable mechanisms may contribute independently to strain differences in behavior. The model predicts that, if the “standard” inter-session interval is shortened from 48 to 24 h, SD rats (but not WKY) will continue to show warm-up; we confirm this prediction in an empirical study with SD and WKY rats. The model further predicts that SD rats will continue to show warm-up with inter-session intervals as short as a few minutes, while WKY rats will not show warm-up, even with inter-session intervals as long as a month. Together, the modeling and empirical data indicate that strain differences in warm-up are qualitative rather than just the result of differential sensitivity to task variables. Understanding the mechanisms that govern expression of warm-up behavior in avoidance may lead to better understanding of pathological avoidance, and potential pathways to modify these processes. PMID

Brain Region-Specific Expression of Genes Mapped within Quantitative Trait Loci for Behavioral Responsiveness to Acute Stress in Fisher 344 and Wistar Kyoto Male Rats (Postprint)

DTIC Science & Technology

2018-03-12

Integrative Genomics Viewer (Broad Institute, Cambridge, Massachusetts), we iden- tified the coding sequence variations between the F344 and WKY... abnormalities and disturbances in brain metabolism resem- bling those in depressive states [74]. Ifna2 is also known to induce memory, concentration, and...Variant and Chronic Interpersonal Stress Prospectively Predicts Social Anxiety and Depression Symptoms Over Six Years. Clinical psychological science

Transcranial direct current stimulation improves short-term memory in an animal model of attention-deficit/hyperactivity disorder.

PubMed

Leffa, Douglas Teixeira; de Souza, Andressa; Scarabelot, Vanessa Leal; Medeiros, Liciane Fernandes; de Oliveira, Carla; Grevet, Eugenio Horacio; Caumo, Wolnei; de Souza, Diogo Onofre; Rohde, Luis Augusto Paim; Torres, Iraci L S

2016-02-01

Attention deficit hyperactivity disorder (ADHD) is characterized by impairing levels of hyperactivity, impulsivity and inattention. However, different meta-analyses have reported disruptions in short and long-term memory in ADHD patients. Previous studies indicate that mnemonic dysfunctions might be the result of deficits in attentional circuits, probably due to ineffective dopaminergic modulation of hippocampal synaptic plasticity. In this study we aimed to evaluate the potential therapeutic effects of a neuromodulatory technique, transcranial direct current stimulation (tDCS), in short-term memory (STM) deficits presented by the spontaneous hypertensive rats (SHR), the most widely used animal model of ADHD. Adult male SHR and Wistar Kyoto rats (WKY) were subjected to a constant electrical current of 0.5 mA intensity applied on the frontal cortex for 20 min/day during 8 days. STM was evaluated with an object recognition test conducted in an open field. Exploration time and locomotion were recorded, and brain regions were dissected to determine dopamine and BDNF levels. SHR spent less time exploring the new object when compared to WKY, and tDCS improved object recognition deficits in SHR without affecting WKY performance. Locomotor activity was higher in SHR and it was not affected by tDCS. After stimulation, dopamine levels were increased in the hippocampus and striatum of both strains, while BDNF levels were increased only in the striatum of WKY. These findings suggest that tDCS on the frontal cortex might be able to improve STM deficits present in SHR, which is potentially related to dopaminergic neurotransmission in the hippocampus and striatum of those animals. Copyright © 2016. Published by Elsevier B.V.

Chronic Blockade of Phosphatidylinositol 3-Kinase in the Nucleus Tractus Solitarii Is Prohypertensive in the Spontaneously Hypertensive Rat

PubMed Central

Zubcevic, Jasenka; Waki, Hidefumi; Diez-Freire, Carlos; Gampel, Alexandra; Raizada, Mohan K.; Paton, Julian F.R.

2009-01-01

Phosphatidylinositol 3-kinase (PI3K) within brain stem neurons has been implicated in hypertension in the spontaneously hypertensive rat (SHR). Previously, we demonstrated elevated expression of PI3K subunits in rostral ventrolateral medulla and paraventricular nucleus of SHRs compared with Wistar-Kyoto rats. Here, we considered expression levels of PI3K in the nucleus tractus solitarii, a pivotal region in reflex regulation of arterial pressure, and determined its functional role for arterial pressure homeostasis in SHRs and Wistar-Kyoto rats. We found elevated mRNA levels of p110β and p110δ catalytic PI3K subunits in the nucleus tractus solitarii of adult (12 to 14 weeks old) SHRs relative to the age-matched Wistar-Kyoto rats (fold differences relative to β-actin: 1.7±0.2 versus 1.01±0.08 for p110β, n=6, P<0.05; 1.62±0.15 versus 1.02±0.1 for p110δ, n=6, P<0.05). After chronic blockade of PI3K signaling in the nucleus tractus solitarii by lentiviral-mediated expression of a mutant form of p85α, systolic pressure increased from 175±3 mm Hg to 191±6 mm Hg (P<0.01) in SHRs but not in Wistar-Kyoto rats. In addition, heart rate increased (from 331±6 to 342±6 bpm; P<0.05) and spontaneous baroreflex gain decreased (from 0.7±0.07 to 0.5±0.04 ms/mm Hg; P<0.001) in the SHRs. Thus, PI3K signaling in the nucleus tractus solitarii of SHR restrains arterial pressure in this animal model of neurogenic hypertension. PMID:19015400

Effects of methylphenidate on attentional set-shifting in a genetic model of attention-deficit/hyperactivity disorder.

PubMed

Cao, Ai-hua; Yu, Lin; Wang, Yu-wei; Wang, Jun-mei; Yang, Le-jin; Lei, Ge-Fei

2012-02-28

Although deficits of attentional set-shifting have been reported in individuals with attention deficit/hyperactivity disorder (ADHD), it is rarely examined in animal models. This study compared spontaneously hypertensive rats (SHRs; a genetic animal model of ADHD) and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats (normoactive control strains), on attentional set-shifting task (ASST) performance. Furthermore, the dose-effects of methylphenidate (MPH) on attentional set-shifting of SHR were investigated. In experiment 1, ASST procedures were conducted in SHR, WKY and SD rats of 8 each at the age of 5 weeks. Mean latencies at the initial phase, error types and numbers, and trials to criteria at each stage were recorded. In experiment 2, 24 SHR rats were randomly assigned to 3 groups of 8 each-- MPH-L (lower dose), MPH-H (higher dose), and SHR-vehicle groups. From 3 weeks, they were administered 2.5 mg/kg or 5 mg/kg MPH or saline respectively for 14 consecutive days. All rats were tested in the ASST at the age of 5 weeks. The SHRs generally exhibited poorer performance on ASST than the control WKY and SD rats. Significant strain effects on mean latency [F (2, 21) = 639.636, p < 0.001] and trials to criterion [F (2, 21) = 114.118, p < 0.001] were observed. The SHRs were found to have more perseverative and regressive errors than the control strains (p < 0.001). After MPH treatment, the two MPH treated groups exhibited significantly longer latency and fewer trials to reach criterion than the SHR-vehicle group and the MPH-L group exhibited fewer trials to reach criterion in more stages compared with the MPH-H group. Significant main effects of treatment [F (2, 21) = 52.174, p < 0.001] and error subtype [F (2, 42) = 221.635, p < 0.01] were found. The SHR may be impaired in discrimination learning, reversal learning and attentional set-shifting. Our study provides evidence that MPH may improve the SHR's performance on attentional set-shifting and lower dose is more

Induced expression of hepatic N-methyl-D-aspartate receptor 2C subunit gene during liver enlargement induced by lead nitrate, a hepatocellular mitogen.

PubMed

Nemoto, Kiyomitsu; Ikeda, Ayaka; Hikida, Tokihiro; Kojima, Misaki; Degawa, Masakuni

2013-02-01

We previously demonstrated the super-induced expression of the Grin2c gene encoding the N-methyl-D-aspartate receptor 2C subunit during the development of liver enlargement with hepatocellular hypertrophy induced by phenobarbital, clofibrate, or piperonyl butoxide. In the present study, we assessed whether or not Grin2c gene expression was induced during the development of chemically induced liver enlargement with hyperplasia. Male Sprague-Dawley (SD) rats, stroke-prone spontaneously hypertensive rats (SHRSPs), and SHRSP's normotensive control, Wistar-Kyoto (WKY) rats, were administered lead nitrate (LN) (0.1 mmol/kg, single i.v.), a direct inducer of liver hyperplasia, and changes in the level of Grin2c mRNA in the liver were assessed by real-time RT-PCR. The level of hepatic Grin2c mRNA was significantly higher 6-48 hr after the injection in SD rats (about 30~40- and 70-fold over the control at 6~24 hr and 48 hr, respectively) and in WKY rats (about 20-fold over the control only at 12 hr), but was not significantly higher in SHRSPs. Such differences in LN-induced levels of Grin2c mRNA among SD rats, WKY rats, and SHRSPs were closely correlated with those in the previously reported increase in liver weight 48 hr after LN administration. The present findings suggest that the increase in the level of hepatic Grin2c mRNA relates to development of chemically induced liver enlargement with hyperplasia.

Characterizing operant hyperactivity in the Spontaneously Hypertensive Rat

PubMed Central

2012-01-01

Background Operant hyperactivity, the emission of reinforced responses at an inordinately high rate, has been reported in children with ADHD and in the Spontaneously Hypertensive Rat (SHR), the most widely studied animal model of ADHD. The SHR emits behavior at hyperactive levels, relative to a normoactive strain, only when such behavior is seldom reinforced. Because of its dependence on rate of reinforcement, operant hyperactivity appears to be driven primarily by incentive motivation, not motoric capacity. This claim was evaluated in the present study using a novel strategy, based on the organization of behavior in bouts of reinforced responses separated by pauses. Method Male SHR, Wistar-Kyoto (WKY) and Wistar rats (WIS) were exposed each to a multiple variable-interval schedule of sucrose reinforcement (12, 24, 48, 96, and 192 s) between post-natal days (PND) 48 and 93. Responding in each schedule was examined in two epochs, PND 58-62 and 89-93. Parameters of response-reinforcement functions (Herrnstein's hyperbola) and bout-organized behavior were estimated in each epoch. Results SHR emitted higher response rates than WKY and WIS, but only when rate of reinforcement was low (fewer than 2 reinforcers per minute), and particularly in the second epoch. Estimates of Herrnstein's hyperbola parameters suggested the primacy of motivational over motoric factors driving the response-rate differential. Across epochs and schedules, a more detailed analysis of response bouts by SHR revealed that these were shorter than those by WKY, but more frequent than those by WKY and WIS. Differences in bout length subsided between epochs, but differences in bout-initiation rate were exacerbated. These results were interpreted in light of robust evidence linking changes in bout-organization parameters and experimental manipulations of motivation and response-reinforcement contingency. Conclusions Operant hyperactivity in SHR was confirmed. Although incentive motivation appears to

Astrocytes from adult Wistar rats aged in vitro show changes in glial functions.

PubMed

Souza, Débora Guerini; Bellaver, Bruna; Raupp, Gustavo Santos; Souza, Diogo Onofre; Quincozes-Santos, André

2015-11-01

Astrocytes, the most versatile cells of the central nervous system, play an important role in the regulation of neurotransmitter homeostasis, energy metabolism, antioxidant defenses and the anti-inflammatory response. Recently, our group characterized cortical astrocyte cultures from adult Wistar rats. In line with that work, we studied glial function using an experimental in vitro model of aging astrocytes (30 days in vitro after reaching confluence) from newborn (NB), adult (AD) and aged (AG) Wistar rats. We evaluated metabolic parameters, such as the glucose uptake, glutamine synthetase (GS) activity, and glutathione (GSH) content, as well as the GFAP, GLUT-1 and xCT expression. AD and AG astrocytes take up less glucose than NB astrocytes and had decreased GLUT1 expression levels. Furthermore, AD and AG astrocytes exhibited decreased GS activity compared to NB cells. Simultaneously, AD and AG astrocytes showed an increase in GSH levels, along with an increase in xCT expression. NB, AD and AG astrocytes presented similar morphology; however, differences in GFAP levels were observed. Taken together, these results improve the knowledge of cerebral senescence and represent an innovative tool for brain studies of aging. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of methylphenidate treatment during adolescence on norepinephrine transporter function in orbitofrontal cortex in a rat model of Attention Deficit Hyperactivity Disorder

PubMed Central

Somkuwar, Sucharita S.; Kantak, Kathleen M.; Dwoskin, Linda P.

2015-01-01

Attention Deficit Hyperactivity Disorder (ADHD) is associated with hypofunctional medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC). Methylphenidate (MPH) remediates ADHD, in part, by inhibiting the norepinephrine transporter (NET). MPH also reduces ADHD-like symptoms in Spontaneously Hypertensive Rats (SHRs), a model of ADHD. However, effects of chronic MPH treatment on NET function in mPFC and OFC in SHR have not been reported. In the current study, long-term effects of repeated treatment with a therapeutically relevant oral dose of MPH during adolescence on NET function in subregions of mPFC (cingulate gyrus, prelimbic cortex and infralimbic cortex) and in the OFC of adult SHR, Wistar-Kyoto (WKY, inbred control) and Wistar (WIS, outbred control) rats were determined using in vivo voltammetry. Following local ejection of norepinephrine (NE), uptake rate was determined as peak amplitude (Amax) x first-order rate constant (k-1). In mPFC subregions, no strain or treatment effects were found in NE uptake rate. In OFC, NE uptake rate in vehicle-treated adult SHR was greater than in adult WKY and WIS administered vehicle. MPH treatment during adolescence normalized NE uptake rate in OFC in SHR. Thus, the current study implicates increased NET function in OFC as an underlying mechanism for reduced noradrenergic transmission in OFC, and consequently, the behavioral deficits associated with ADHD. MPH treatment during adolescence normalized NET function in OFC in adulthood, suggesting that the therapeutic action of MPH persists long after treatment cessation and may contribute to lasting reductions in deficits associated with ADHD. PMID:25680322

D-Galactose High-Dose Administration Failed to Induce Accelerated Aging Changes in Neurogenesis, Anxiety, and Spatial Memory on Young Male Wistar Rats.

PubMed

Cardoso, Armando; Magano, Sara; Marrana, Francisco; Andrade, José P

2015-12-01

The model of accelerated senescence with the prolonged administration of d-galactose is used in anti-aging studies because it mimics several aging-associated alterations such as increase of oxidative stress and decline of cognition. However, there is no standardized protocol for this aging model, and recently some reports have questioned its effectiveness. To clarify this issue, we used a model of high-dose d-galactose on 1-month-old male Wistar rats and studied the hippocampus, one of the most affected brain regions. In one group (n = 10), d-galactose was daily administered intraperitoneally (300 mg/kg) during 8 weeks whereas age-matched controls (n = 10) were injected intraperitoneally with saline. A third group (n = 10) was treated with the same dose of d-galactose and with oral epigallocatechin-3-gallate (EGCG) (2 grams/L), a green tea catechin with anti-oxidant and neuroprotective properties. After treatments, animals were submitted to open-field, elevated plus-maze and Morris water maze tests, and neurogenesis in the dentate gyrus subgranular layer was quantified. There were no significant alterations when the three groups were compared in the number of doublecortin- and Ki-67-immunoreactive cells, and also on anxiety levels, spatial learning, and memory. Therefore, d-galactose was not effective in the induction of accelerated aging, and EGCG administered to d-galactose-treated animals did not improve behavior and had no effects on neurogenesis. We conclude that daily 300 mg/kg of d-galactose administered intraperitoneally may not be a suitable model for inducing age-related neurobehavioral alterations in young male Wistar rats. More studies are necessary to obtain a reliable and reproducible model of accelerated senescence in rodents using d-galactose.

No involvement of the nerve growth factor gene locus in hypertension in spontaneously hypertensive rats.

PubMed

Nemoto, Kiyomitsu; Sekimoto, Masashi; Fukamachi, Katsumi; Kageyama, Haruaki; Degawa, Masakuni; Hamadai, Masanori; Hendley, Edith D; Macrae, I Mhairi; Clark, James S; Dominiczak, Anna F; Ueyama, Takashi

2005-02-01

Sympathetic hyper-innervation and increased levels of nerve growth factor (NGF), an essential neurotrophic factor for sympathetic neurons, have been observed in the vascular tissues of spontaneously hypertensive rats (SHRs). Such observations have suggested that the pathogenesis of hypertension might involve a qualitative or quantitative abnormality in the NGF protein, resulting from a significant mutation in the gene's promoter or coding region. In the present study, we analyzed the nucleotide sequences of the cis-element of the NGF gene in SHRs, stroke-prone SHRs (SHRSPs), and normotensive Wistar-Kyoto (WKY) rats. The present analyses revealed some differences in the 3-kb promoter region, coding exon, and 3' untranslated region (3'UTR) for the NGF gene among those strains. However, the observed differences did not lead to changes in promoter activity or to amino acid substitution; nor did they represent a link between the 3'UTR mutation of SHRSPs and elevated blood pressure in an F2 generation produced by crossbreeding SHRSPs with WKY rats. These results suggest that the NGF gene locus is not involved in hypertension in SHR/ SHRSP strains. The present study also revealed two differences between SHRs and WKY rats, as found in cultured vascular smooth muscle cells and in mRNA prepared from each strain. First, SHRs had higher expression levels of c-fos and c-jun genes, which encode the component of the AP-1 transcription factor that activates NGF gene transcription. Second, NGF mRNAs prepared from SHRs had a longer 3'UTR than those prepared from WKY rats. Although it remains to be determined whether these events play a role in the hypertension of SHR/SHRSP strains, the present results emphasize the importance of actively searching for aberrant trans-acting factor(s) leading to the enhanced expression of the NGF gene and NGF protein in SHR/SHRSP strains.

IGF-1 receptor cleavage in hypertension.

PubMed

Cirrik, Selma; Schmid-Schönbein, Geert W

2018-06-01

Increased protease activity causes receptor dysfunction due to extracellular cleavage of different membrane receptors in hypertension. The vasodilatory effects of insulin-like growth factor-1 (IGF-1) are decreased in hypertension. Therefore, in the present study the association of an enhanced protease activity and IGF-1 receptor cleavage was investigated using the spontaneously hypertensive rats (SHRs) and their normotensive Wistar Kyoto (WKY) controls (n = 4). Matrix metalloproteinase (MMP) activities were determined using gelatin zymography on plasma and different tissue samples. WKY aorta rings were incubated in WKY or SHR plasma with or without MMP inhibitors, and immunohistochemistry was used to quantify the densities of the alpha and beta IGF-1 receptor (IGF-1R) subunits and to determine receptor cleavage. The pAkt and peNOS levels in the aorta were investigated using immunoblotting as a measure of IGF-IR function. Increased MMP-2 and MMP-9 activities were detected in plasma and peripheral tissues of SHRs. IGF-1R beta labeling was similar in both groups without plasma incubation, but the fraction of immunolabeled area for IGF-1R alpha was lower in the endothelial layer of the SHR aorta (p < 0.05). A 24-h incubation of WKY aorta with SHR plasma did not affect the IGF-1R beta labeling density, but reduced the IGF-1R alpha labeling density in the endothelium (p < 0.05). MMP inhibitors prevented this decrease (p < 0.01). Western blot analyses revealed that the pAkt and peNOS levels under IGF-1-stimulated and -unstimulated conditions were lower in SHRs (p < 0.05). A reduced IGF-1 cellular response in the aorta was associated with the decrease in the IGF-1R alpha subunit in the SHR hypertension model. Our results indicate that MMP-dependent receptor cleavage contributed to the reduced IGF-1 response in SHRs.

Modulation of enteric neurons by interleukin-6 and corticotropin-releasing factor contributes to visceral hypersensitivity and altered colonic motility in a rat model of irritable bowel syndrome

PubMed Central

Buckley, Maria M; O'Halloran, Ken D; Rae, Mark G; Dinan, Timothy G; O'Malley, Dervla

2014-01-01

Abstract The search for effective therapeutic strategies for irritable bowel syndrome (IBS) is hampered by an incomplete understanding of its underlying pathophysiology. Stress and altered plasma cytokine profiles indicative of immune activation are characteristic of the disorder. The neuromodulatory effects of interleukin-6 (IL-6) and corticotropin-releasing factor receptor (CRFR) 1 in visceral pain and stress-induced defecation in the Wistar Kyoto (WKY) rat model of IBS were investigated. Sprague Dawley and WKY rats were administered anti-IL-6 receptor antibodies (xIL-6R, 0.5 mg kg−1 i.p) with or without the CRFR1 antagonist antalarmin (10 mg kg−1 i.p). Post-intervention, the pain threshold to colorectal distension and stress-induced faecal output were compared and changes in colonic mucosal protein expression were investigated. The neuro-stimulatory effects of IBS plasma on the myenteric plexus is mediated by IL-6, IL-8 and CRF. The stimulatory effects of these soluble factors on myenteric neuron excitability and colonic contractility were additive. Moreover, inhibition of IL-6 and CRF1 receptors in vivo in the WKY IBS rat model normalized stress-induced defecation (P < 0.01) and visceral pain sensitivity (P < 0.001) with associated changes in protein expression of the tight junction proteins occludin and claudin 2, the visceral pain-associated T-type calcium channel CaV3.2 and intracellular signalling molecules STAT3, SOCS3 and ERK1/2. These studies demonstrate the additive effects of immune and stress factors on myenteric neuronal excitability. Moreover, combined targeting of peripheral IL-6 and CRF1 receptors is effective in alleviating IBS-like symptoms in the WKY rat. Thus, crosstalk between stress and immune factors during IBS flares may underlie symptom exacerbation. PMID:25260633

Cellular distribution of calcium current is unaltered during compensated hypertrophy in the spontaneously hypertensive rat.

PubMed

Fowler, Mark R; Orchard, Clive H; Harrison, Simon M

2007-01-01

Changes in cellular calcium (Ca(2+)) handling are thought to underlie the altered contraction that occurs during cardiac hypertrophy and failure. Recent work has highlighted the importance of t-tubules in the control of intracellular Ca(2+). The present study was performed to investigate whether changes in the distribution of I (Ca) between the surface and t-tubule membranes might contribute to the altered Ca(2+) handling observed during compensated hypertrophy in the spontaneously hypertensive rat (SHR). Experiments were performed on ventricular myocytes isolated from 5-month-old SHR and normotensive Wistar-Kyoto (WKY) control rats. Osmotic shock using formamide was used to disrupt the t-tubular system and the whole-cell patch clamp technique used to monitor I (Ca) in the presence and absence of t-tubules. Membrane capacitance and I (Ca) were greater in control SHR than WKY myocytes; following detubulation, cell capacitance and I (Ca) both decreased and were no longer significantly different in the two cell types. The density of I (Ca) was not significantly different in control SHR and WKY cells or in detubulated myocytes from the two species. These data suggest that the distribution of I (Ca) is unchanged in SHR myocytes compared to WKY controls; I (Ca) density in the t-tubules was 1.2-fold greater than in the sarcolemma in both strains. These data also imply that the increase in surface area in SHR myocytes is due principally to an increase in t-tubular area, which is accompanied by an approximately equivalent increase in I (Ca), so that the density of I (Ca) at the cell surface and in the t-tubules remains the same. These changes would be expected to retain cell function and synchronicity of Ca(2+) release in the SHR at this stage of compensated hypertrophy.

Effects of chronic N-acetylcysteine treatment on the actions of peroxynitrite on aortic vascular reactivity in hypertensive rats.

PubMed

Cabassi, A; Dumont, E C; Girouard, H; Bouchard, J F; Le Jossec, M; Lamontagne, D; Besner, J G; de Champlain, J

2001-07-01

Peroxynitrite (ONOO-), the product of superoxide and nitric oxide, seems to be involved in vascular alterations in hypertension. To evaluate the effects of ONOO- on endothelium-dependent and independent aortic vascular responsiveness, oxidized/reduced glutathione balance (GSSG/GSH), malondialdehyde aortic content, and the formation of 3-nitrotyrosine (3-NT), a stable marker of ONOO-, in N-acetylcysteine (NAC)-treated normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). In SHR only, NAC significantly reduced heart rate and systolic, but not diastolic, blood pressure. It also improved endothelium-dependent aortic relaxation in SHR, but not after exposure to ONOO-. Endothelium-dependent and independent aortic relaxations were markedly impaired by ONOO- in both strains of rat. NAC partially protected SHR against the ONOO- -induced reduction in endothelium-independent relaxation. Aortic GSSG/GSH ratio and malondialdehyde, which were higher in SHR than in WKY rats, showed a greater increase in SHR after exposure to ONOO-. NAC decreased GSSG/GSH and malondialdehyde in both strains of rat before and after exposure to ONOO-. The 3-NT concentration, which was similar in both strains of rat under basal conditions, was greater in SHR than in WKY rats after the addition of ONOO-, with a reduction only in NAC-treated SHR. These findings suggest an increased vulnerability of SHR aortas to the effects of ONOO- as compared with those of WKY rats. The selective improvements produced by NAC, in systolic arterial pressure, heart rate, aortic endothelial function, ONOO- -induced impairment of endothelium-independent relaxation, aortic GSSG/GSH balance, malondialdehyde content and 3-NT formation in SHR suggest that chronic administration of NAC may have a protective effect against aortic vascular dysfunction in the SHR model of hypertension.

C4d Deposition and Cellular Infiltrates as Markers of Acute Rejection in Rat Models of Orthotopic Lung Transplantation

PubMed Central

Murata, Kazunori; Iwata, Takekazu; Nakashima, Shinji; Fox-Talbot, Karen; Qian, Zhiping; Wilkes, David S.; Baldwin, William M.

2008-01-01

Background C4d is a useful marker of antibody-mediated rejection in cardiac and renal transplants, but clinical studies examining correlations between circulating alloantibodies, C4d deposition, and rejection in lung transplants have yielded conflicting results. Methods We studied circulating alloantibody levels and C4d deposition in two rat models of lung transplantation: Brown Norway (BN) to Wistar-Kyoto (WKY) and PVG.R8 to PVG.1U lung allografts. The availability of C6 deficient (C6−) and C6 sufficient (C6+) PVG 1U rats allowed evaluation of the effects of the terminal complement components on graft injury and C4d deposition. Results The lung allografts had histologic features resembling human posttransplant capillaritis, characterized by neutrophilic infiltration of alveoli, edema, and hemorrhage. Immunoperoxidase stains on cross sections of allografts showed intense, diffuse, C4d deposition in a continuous linear pattern on the vascular endothelium. C4d deposits were found in both BN to WKY and PVG R8 to 1U allografts, whereas no staining was detectable in WKY to WKY isografts or native lungs. Complement deposition was associated with vascular disruption in C6−, but not in C6+ recipients. The presence of circulating donor-specific alloantibodies was verified by flow cytometry. Cell-specific staining revealed perivascular accumulation of macrophages and T lymphocytes whereas neutrophils were sequestered in the intravascular and alveolar capillary compartments. Conclusions The deposition of C4d on vascular endothelium as well as the coincident presence of alloantibodies is consistent with previous findings in antibody-mediated rejection of renal and cardiac transplants. Furthermore, the histological features of our allografts support the concept that posttransplant capillaritis is a form of humoral rejection. PMID:18622289

GPER mediates cardiotropic effects in spontaneously hypertensive rat hearts.

PubMed

De Francesco, Ernestina Marianna; Angelone, Tommaso; Pasqua, Teresa; Pupo, Marco; Cerra, Maria Carmela; Maggiolini, Marcello

2013-01-01

Estrogens promote beneficial effects in the cardiovascular system mainly through the estrogen receptor (ER)α and ERβ, which act as ligand-gated transcription factors. Recently, the G protein-coupled estrogen receptor (GPER) has been implicated in the estrogenic signaling in diverse tissues, including the cardiovascular system. In this study, we demonstrate that left ventricles of male Spontaneously Hypertensive Rats (SHR) express higher levels of GPER compared to normotensive Wistar Kyoto (WKY) rats. In addition, we show that the selective GPER agonist G-1 induces negative inotropic and lusitropic effects to a higher extent in isolated and Langendorff perfused hearts of male SHR compared to WKY rats. These cardiotropic effects elicited by G-1 involved the GPER/eNOS transduction signaling, as determined by using the GPER antagonist G15 and the eNOS inhibitor L-NIO. Similarly, the G-1 induced activation of ERK1/2, AKT, GSK3β, c-Jun and eNOS was abrogated by G15, while L-NIO prevented only the eNOS phosphorylation. In hypoxic Langendorff perfused WKY rat heart preparations, we also found an increased expression of GPER along with that of the hypoxic mediator HIF-1α and the fibrotic marker CTGF. Interestingly, G15 and L-NIO prevented the ability of G-1 to down-regulate the expression of both HIF-1α and CTGF, which were found expressed to a higher extent in SHR compared to WKY rat hearts. Collectively, the present study provides novel data into the potential role played by GPER in hypertensive disease on the basis of its involvement in myocardial inotropism and lusitropism as well as the expression of the apoptotic HIF-1α and fibrotic CTGF factors. Hence, GPER may be considered as a useful target in the treatment of some cardiac dysfunctions associated with stressful conditions like the essential hypertension.

Na2S, a fast-releasing H2S donor, given as suppository lowers blood pressure in rats.

PubMed

Tomasova, Lenka; Drapala, Adrian; Jurkowska, Halina; Wróbel, Maria; Ufnal, Marcin

2017-10-01

Hydrogen sulfide (H 2 S) is involved in blood pressure control. The available slow-releasing H 2 S-donors are poorly soluble in water and their ability to release H 2 S in biologically relevant amounts under physiological conditions is questionable. Therefore, new slow-releasing donors or new experimental approaches to fast-releasing H 2 S donors are needed. Hemodynamics and ECG were recorded in male, anesthetized Wistar Kyoto rats (WKY) and in Spontaneously hypertensive rats (SHR) at baseline and after: 1) intravenous (iv) infusion of vehicle or Na 2 S; 2) administration of vehicle suppositories or Na 2 S suppositories. Intravenously administered vehicle and vehicle suppositories did not affect mean arterial blood pressure (MABP) and heart rate (HR). Na 2 S administered iv caused a significant, but transient (2-5min) decrease in MABP. Na 2 S suppositories produced a dose-dependent hypotensive response that lasted ∼45min in WKY and ∼75-80min in SHR. It was accompanied by a decrease in HR in WKY, and an increase in HR in SHR. Na 2 S suppositories did not produce a significant change in corrected QT, an indicator of cardiotoxicity. Na 2 S suppositories increased blood level of thiosulfates, products of H 2 S oxidation. Na 2 S administered in suppositories exerts a prolonged hypotensive effect in rats, with no apparent cardiotoxic effect. SHR and WKY differ in hemodynamic response to the H 2 S donor. Suppository formulation of fast-releasing H 2 S donors may be useful in research, if a reference slow-releasing H 2 S donor is not available. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Super, Red Palm and Palm Oleins Improve the Blood Pressure, Heart Size, Aortic Media Thickness and Lipid Profile in Spontaneously Hypertensive Rats

PubMed Central

Boon, Chee-Meng; Ng, Mei-Han; Choo, Yuen-May; Mok, Shiueh-Lian

2013-01-01

Background Oleic acid has been shown to lower high blood pressure and provide cardiovascular protection. Curiosity arises as to whether super olein (SO), red palm olein (RPO) and palm olein (PO), which have high oleic acid content, are able to prevent the development of hypertension. Methodology/Principal Findings Four-week-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were fed 15% SO, RPO or PO supplemented diet for 15 weeks. After 15 weeks of treatment, the systolic blood pressure (SBP) of SHR treated with SO, RPO and PO were 158.4±5.0 mmHg (p<0.001), 178.9±2.7 mmHg (p<0.001) and 167.7±2.1 mmHg (p<0.001), respectively, compared with SHR controls (220.9±1.5 mmHg). Bradycardia was observed with SO and PO. In contrast, the SBP and heart rate of treated WKY rats were not different from those of WKY controls. The SO and PO significantly reduced the increased heart size and thoracic aortic media thickness observed in untreated SHR but RPO reduced only the latter. No such differences, however, were observed between the treated and untreated WKY rats. Oil Red O enface staining of thoracic-abdominal aorta did not show any lipid deposition in all treated rats. The SO and RPO significantly raised serum alkaline phosphatase levels in the SHR while body weight and renal biochemical indices were unaltered in both strains. Serum lipid profiles of treated SHR and WKY rats were unchanged, with the exception of a significant reduction in LDL-C level and total cholesterol/HDL ratio (atherogenic index) in SO and RPO treated SHR compared with untreated SHR. Conclusion The SO, RPO and PO attenuate the rise in blood pressure in SHR, accompanied by bradycardia and heart size reduction with SO and PO, and aortic media thickness reduction with SO, RPO and PO. The SO and RPO are antiatherogenic in nature by improving blood lipid profiles in SHR. PMID:23409085

Reduced L-Carnitine Transport in Aortic Endothelial Cells from Spontaneously Hypertensive Rats

PubMed Central

Salsoso, Rocío; Guzmán-Gutiérrez, Enrique; Arroyo, Pablo; Salomón, Carlos; Zambrano, Sonia; Ruiz-Armenta, María Victoria; Blanca, Antonio Jesús; Pardo, Fabián; Leiva, Andrea; Mate, Alfonso; Sobrevia, Luis; Vázquez, Carmen María

2014-01-01

Impaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Carnitine transport is mainly mediated by novel organic cation transporters 1 (Octn1, Na+-independent) and 2 (Octn2, Na+-dependent); however, their kinetic properties and potential consequences in hypertension are unknown. We hypothesize that L-carnitine transport kinetic properties will be altered in aortic endothelium from spontaneously hypertensive rats (SHR). L-Carnitine transport was measured at different extracellular pH (pHo 5.5–8.5) in the absence or presence of sodium in rat aortic endothelial cells (RAECs) from non-hypertensive Wistar-Kyoto (WKY) rats and SHR. Octn1 and Octn2 mRNA relative expression was also determined. Dilation of endothelium-intact or denuded aortic rings in response to calcitonine gene related peptide (CGRP, 0.1–100 nmol/L) was measured (myography) in the absence or presence of L-carnitine. Total L-carnitine transport was lower in cells from SHR compared with WKY rats, an effect due to reduced Na+-dependent (Na+ dep) compared with Na+-independent (Na+ indep) transport components. Saturable L-carnitine transport kinetics show maximal velocity (V max), without changes in apparent K m for Na+ indep transport in SHR compared with WKY rats. Total and Na+ dep component of transport were increased, but Na+ indep transport was reduced by extracellular alkalization in WKY rats. However, alkalization reduced total and Na+ indep transport in cells from SHR. Octn2 mRNA was higher than Octn-1 mRNA expression in cells from both conditions. Dilation of artery rings in response to CGRP was reduced in vessels from SHR compared with WKY rats. CGRP effect was endothelium-dependent and restored by L-carnitine. All together these results suggest that reduced

An elevation in physical coupling of type 1 inositol 1,4,5-trisphosphate (IP3) receptors to transient receptor potential 3 (TRPC3) channels constricts mesenteric arteries in genetic hypertension.

PubMed

Adebiyi, Adebowale; Thomas-Gatewood, Candice M; Leo, M Dennis; Kidd, Michael W; Neeb, Zachary P; Jaggar, Jonathan H

2012-11-01

Hypertension is associated with an elevation in agonist-induced vasoconstriction, but mechanisms involved require further investigation. Many vasoconstrictors bind to phospholipase C-coupled receptors, leading to an elevation in inositol 1,4,5-trisphosphate (IP(3)) that activates sarcoplasmic reticulum IP(3) receptors. In cerebral artery myocytes, IP(3) receptors release sarcoplasmic reticulum Ca(2+) and can physically couple to canonical transient receptor potential 3 (TRPC3) channels in a caveolin-1-containing macromolecular complex, leading to cation current activation that stimulates vasoconstriction. Here, we investigated mechanisms by which IP(3) receptors control vascular contractility in systemic arteries and IP(3)R involvement in elevated agonist-induced vasoconstriction during hypertension. Total and plasma membrane-localized TRPC3 protein was ≈2.7- and 2-fold higher in mesenteric arteries of spontaneously hypertensive rats (SHRs) than in Wistar-Kyoto (WKY) rat controls, respectively. In contrast, IP(3)R1, TRPC1, TRPC6, and caveolin-1 expression was similar. TRPC3 expression was also similar in arteries of pre-SHRs and WKY rats. Control, IP(3)-induced and endothelin-1 (ET-1)-induced fluorescence resonance energy transfer between IP3R1 and TRPC3 was higher in SHR than WKY myocytes. IP3-induced cation current was ≈3-fold larger in SHR myocytes. Pyr3, a selective TRPC3 channel blocker, and calmodulin and IP(3) receptor binding domain peptide, an IP(3)R-TRP physical coupling inhibitor, reduced IP(3)-induced cation current and ET-1-induced vasoconstriction more in SHR than WKY myocytes and arteries. Thapsigargin, a sarcoplasmic reticulum Ca(2+)-ATPase blocker, did not alter ET-1-stimulated vasoconstriction in SHR or WKY arteries. These data indicate that ET-1 stimulates physical coupling of IP(3)R1 to TRPC3 channels in mesenteric artery myocytes, leading to vasoconstriction. Furthermore, an elevation in IP(3)R1 to TRPC3 channel molecular coupling augments

An Elevation in Physical Coupling of Type 1 IP3 Receptors to TRPC3 Channels Constricts Mesenteric Arteries in Genetic Hypertension

PubMed Central

Adebiyi, Adebowale; Thomas-Gatewood, Candice M.; Leo, M. Dennis; Kidd, Michael W.; Neeb, Zachary P.; Jaggar, Jonathan H.

2013-01-01

Hypertension is associated with an elevation in agonist-induced vasoconstriction, but mechanisms involved require further investigation. Many vasoconstrictors bind to phospholipase C-coupled receptors, leading to an elevation in inositol 1,4,5-trisphosphate (IP3) that activates sarcoplasmic reticulum (SR) IP3 receptors (IP3Rs). In cerebral artery myocytes, IP3Rs release SR Ca2+ and can physically couple to canonical transient receptor potential 3 (TRPC3) channels in a caveolin-1-containing macromolecular complex, leading to cation current (ICat) activation that stimulates vasoconstriction. Here, we investigated mechanisms by which IP3Rs control vascular contractility in systemic arteries and IP3R involvement in elevated agonist-induced vasoconstriction during hypertension. Total and plasma membrane-localized TRPC3 protein was ~2.7- and 2-fold higher in mesenteric arteries of hypertensive spontaneously hypertensive rats (SHR) than in Wistar-Kyoto (WKY) rat controls, respectively. In contrast, IP3R1, TRPC1, TRPC6, and caveolin-1 expression was similar. TRPC3 expression was also similar in arteries of pre-hypertensive SHR and WKY rats. Control, IP3- and endothelin-1 (ET-1)-induced FRET between IP3R1 and TRPC3 was higher in hypertensive SHR than WKY myocytes. IP3-induced ICat was ~3-fold larger in SHR myocytes. Pyr3, a selective TRPC3 channel blocker, and CIRBP-TAT, an IP3R-TRP physical coupling inhibitor, reduced IP3-induced ICat and ET-1-induced vasoconstriction more in SHR than WKY myocytes and arteries. Thapsigargin, a SR Ca2+-ATPase blocker, did not alter ET-1-stimulated vasoconstriction in SHR or WKY arteries. These data indicate that ET-1 stimulates physical coupling of IP3R1 to TRPC3 channels in mesenteric artery myocytes, leading to vasoconstriction. Furthermore, an elevation in IP3R1 to TRPC3 channel molecular coupling augments ET-1-induced vasoconstriction during hypertension. PMID:23045459

Honey Supplementation in Spontaneously Hypertensive Rats Elicits Antihypertensive Effect via Amelioration of Renal Oxidative Stress

PubMed Central

Erejuwa, Omotayo O.; Sulaiman, Siti A.; Ab Wahab, Mohd S.; Sirajudeen, Kuttulebbai N. S.; Salleh, Salzihan; Gurtu, Sunil

2012-01-01

Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY) rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA) levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione S-transferase (GST) were significantly downregulated while total antioxidant status (TAS) and activities of GST and catalase (CAT) were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR. PMID:22315654

Distinct alterations in colonic morphology and physiology in two rat models of enhanced stress-induced anxiety and depression-like behaviour.

PubMed

O'Malley, Dervla; Julio-Pieper, Marcela; Gibney, Sinead M; Dinan, Timothy G; Cryan, John F

2010-03-01

Stress and anxiety are important causal and exacerbating factors in functional gastro-intestinal (GI) disorders such as irritable bowel syndrome. Stress affects GI motility, faecal transit and visceral pain sensitivity. Additionally, permeability and function of the gut epithelium, which acts as a barrier between the external environment and the body's internal milieu is altered by stress. However, the effects of an enhanced stress response on colonic morphology require further investigation. We have used two animal models of stress and anxiety, the maternally separated (MS) and Wistar Kyoto (WKY) rats to examine colonic morphology. These rats exhibit increased anxiety behaviours, visceral hypersensitivity and increased stress-induced defecation in the open field arena. At a morphological level, increased mucus secretion and an associated elevation in the number of mucosal goblet cells was observed in the high anxiety rats. Additionally, the mucosal layer was flattened in MS and WKY rats, a finding indicative of mild mucosal damage. Furthermore, the muscular layer of the distal colon in these animals was thickened, an observation that may have implications for faecal transit and visceral pain perception. This study provides evidence of altered colonic function and morphology in two animal models with a heightened response to stress.

Honey supplementation in spontaneously hypertensive rats elicits antihypertensive effect via amelioration of renal oxidative stress.

PubMed

Erejuwa, Omotayo O; Sulaiman, Siti A; Ab Wahab, Mohd S; Sirajudeen, Kuttulebbai N S; Salleh, Salzihan; Gurtu, Sunil

2012-01-01

Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY) rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA) levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione S-transferase (GST) were significantly downregulated while total antioxidant status (TAS) and activities of GST and catalase (CAT) were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR.

Increased noradrenergic activity in prefrontal cortex slices of an animal model for attention-deficit hyperactivity disorder--the spontaneously hypertensive rat.

PubMed

Russell, V; Allie, S; Wiggins, T

2000-12-20

Spontaneously hypertensive rats (SHR) are used as a model for attention-deficit/hyperactivity disorder (ADHD) since SHR are hyperactive and they show defective sustained attention in behavioral tasks. Using an in vitro superfusion technique we showed that norepinephrine (NE) release from prefrontal cortex slices of SHR was not different from that of their Wistar-Kyoto (WKY) control rats when stimulated either electrically or by exposure to buffer containing 25 mM K(+). The monoamine vesicle transporter is, therefore, unlikely to be responsible for the deficiency in DA observed in SHR, since, in contrast to DA, vesicle stores of NE do not appear to be depleted in SHR. In addition, alpha(2)-adrenoceptor mediated inhibition of NE release was reduced in SHR, suggesting that autoreceptor function was deficient in prefrontal cortex of SHR. So, while DA neurotransmission appears to be down-regulated in SHR, the NE system appears to be under less inhibitory control than in WKY suggesting hypodopaminergic and hypernoradrenergic activity in prefrontal cortex of SHR. These findings are consistent with the hypothesis that the behavioral disturbances of ADHD are the result of an imbalance between NE and DA systems in the prefrontal cortex, with inhibitory DA activity being decreased and NE activity increased relative to controls.

New insights into the pathogenesis of glucocorticoid-induced avascular necrosis: microarray analysis of gene expression in a rat model

PubMed Central

2010-01-01

Introduction Avascular necrosis of the femoral head (ANFH) occurs variably after exposure to corticosteroids. Microvascular thrombosis is a common pathological finding. Since systemic thrombophilia is only weakly linked with ANFH, we propose that microvascular vessel pathology may be more related to local endothelial dysfunction and femoral head apoptosis. Corticosteroid effects on the endothelium and resultant apoptosis have been reported. We hypothesize that corticosteroids contribute to a differential gene expression in the femoral head in rats with early ANFH. Methods Besides bone marrow necrosis, which is a common sign in ANFH and reported in the early stages, we include the presence of apoptosis in this study as a criterion for diagnosing early disease. Forty Wistar Kyoto (WKY) rats were randomized to either a corticosteroid-treated group or an age-matched control group for six months. After sacrifice, the femoral heads were examined for ANFH. Total mRNA was extracted from femoral heads. Affymetrix exon array (Santa Clara, CA, USA) was performed on 15 selected RNA samples. Validation methods included RT-PCR and immunohistochemistry (IHC). Results Although rat exon array demonstrated a significant upregulation of 51 genes (corticosteroid(+)/ANFH(+) VS control), alpha-2-macroglobulin (A2M) gene was particularly over-expressed. Results were validated by RT-PCR and IHC. Importantly, A2M is known to share vascular, osteogenic and cartilage functions relevant for ANFH. Conclusions The findings suggest that corticosteroid-induced ANFH in rats might be mediated by A2M. Investigation of A2M as a potential marker, and a treatment target, for early ANFH should be carried out. PMID:20579363

Effects of fosinopril and losartan on renal Klotho expression and oxidative stress in spontaneously hypertensive rats.

PubMed

Tang, Rong; Zhou, Qiaoling; Liu, Zhichun; Xiao, Zhou; Pouranan, Veeraragoo

2011-01-01

To explore effects of fosinopril and losartan on renal Klotho expression and oxidative stress in spontaneously hypertensive rats (SHR) and the mechanisms underlying the protection against renal damage. Fifteen male SHRs (22 weeks old) were randomly divided into 3 groups (n=5 in each group): a SHR group, a fosinopril group [10 mg/(kg.d)], and a losartan group [50 mg/(kg.d)]. Age-matched Wistar-Kyoto (WKY) rats were chosen for a control group. Eight weeks later, tail arterial pressure, 24 hours urinary protein (Upro),urinary N-acetyl-β-D-glucosaminidase (NAGase) were measured. Renal pathological changes were examined under light microscopy by HE staining. The renal mRNA and protein expression of Klotho were determined by RT-PCR, immunohistochemical staining or Western blot. The levels of total antioxidant capacity (TAOC), malondialdehyde (MDA), Cu/Zn superoxide dismutase (Cu/Zn-SOD), Mn superoxide dismutase (Mn-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined. The typical pathological characteristics of hypertensive renal damage were observed in the kidney of the SHR group.Compared with the SHR group, the systolic pressure, Upro, and urinary NAGase, the content of MDA and renal pathological damage was reduced while the renal Klotho expression and activities of TAOC, Cu/Zn-SOD, CAT, and GSH-Px were increased (P<0.05 or P<0.01) in the fosinopril or losartan group. There was no significant difference in renal Mn-SOD level among the 4 groups (P>0.05). Fosinopril and losartan can exert protection against hypertensive renal damage through upregulating Klotho expression as well as reducing oxidative stress.

COMPARISON OF CARDIOPULMONARY RESPONSES OF WISTAR KYOTO (WKY) AND STROKE PRONE SPONTANEOUSLY HYPERTENSIVE RATS (SHRSP) TO PARTICULATE MATTER (PM) EXPOSURE

EPA Science Inventory

Although a clear link between cardiopulmonary disease and an increased susceptibility to air pollution has been established epidemiologically, the mechanistic link remains undefined. Animal models of disease are widely used to investigate this link. Here we compare the cardiopu...

Rearing in an enriched environment attenuated hyperactivity and inattention in the Spontaneously Hypertensive Rats, an animal model of Attention-Deficit Hyperactivity Disorder.

PubMed

Botanas, Chrislean Jun; Lee, Hyelim; de la Peña, June Bryan; Dela Peña, Irene Joy; Woo, Taeseon; Kim, Hee Jin; Han, Doug Hyun; Kim, Bung-Nyun; Cheong, Jae Hoon

2016-03-01

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, characterized by symptoms of hyperactivity, inattention, and impulsivity. It is commonly treated with psychostimulants that typically begins during childhood and lasts for an extended period of time. However, there are concerns regarding the consequences of chronic psychostimulant treatment; thus, there is a growing search for an alternative management for ADHD. One non-pharmacological management that is gaining much interest is environmental enrichment. Here, we investigated the effects of rearing in an enriched environment (EE) on the expression of ADHD-like symptoms in the Spontaneously Hypertensive Rats (SHRs), an animal model of ADHD. SHRs were reared in EE or standard environment (SE) from post-natal day (PND) 21 until PND 49. Thereafter, behavioral tests that measure hyperactivity (open field test [OFT]), inattention (Y-maze task), and impulsivity (delay discounting task) were conducted. Additionally, electroencephalography (EEG) was employed to assess the effects of EE on rat's brain activity. Wistar-Kyoto (WKY) rats, the normotensive counterpart of the SHRs, were used to determine whether the effects of EE were specific to a particular genetic background. EE improved the performance of the SHRs and WKY rats in the OFT and Y-maze task, but not the delay discounting task. Interestingly, EE induced significant EEG changes in WKY rats, but not in the SHRs. These findings show that rearing environment may play a role in the expression of ADHD-like symptoms in the SHRs and that EE may be considered as a putative complementary approach in managing ADHD symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

Influence of acute progressive hypoxia on cardiovascular variability in conscious spontaneously hypertensive rats

PubMed Central

Sugimura, Mitsutaka; Hirose, Yohsuke; Hanamoto, Hiroshi; Okada, Kenji; Boku, Aiji; Morimoto, Yoshinari; Taki, Kunitaka; Niwa, Hitoshi

2008-01-01

The purpose of this study is to examine the influence of acute progressive hypoxia on cardiovascular variability and striatal dopamine (DA) levels in conscious, spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). After preparation for measurement, the inspired oxygen concentration of rats was decreased to 10% within 5 min (descent stage), maintained at 10% for 10 min (fixed stage), and then elevated back to 20% over 5 min (recovery stage). The systolic blood pressure (SBP) and heart rate (HR) variability at each stage was calculated to evaluate the autonomic nervous system response using the wavelet method. Striatal DA during each stage was measured using in vivo microdialysis. We found that SHR showed a more profound hemodynamic response to progressive hypoxia as compared to WKY. Cardiac parasympathetic activity in SHR was significantly inhibited by acute progressive hypoxia during all stages, as shown by the decrease in the high frequency band of HR variability (HR-HF), along with transient increase in sympathetic activity during the early hypoxic phase. This decrease in the HR-HF continued even when SBP was elevated. Striatal DA levels showed the transient similar elevation in both groups. These findings suggest that acute progressive hypoxic stress in SHR inhibits cardiac parasympathetic activity through reduction of baroreceptor reflex sensitivity, with potentially severe deleterious effects on circulation, in particular on HR and circulatory control. Furthermore, it is thought that the influence of acute progressive hypoxia on striatal DA levels is similar in SHR and WKY. PMID:18599365

Enhanced expression of endothelial nitric oxide synthase in the myocardium ameliorates the progression of left ventricular hypertrophy in L-arginine treated Wistar-Kyoto rats.

PubMed

Ahmad, A; Sattar, M A; Rathore, H A; Abdulla, M H; Khan, S A; Abdullah, N A; Johns, E J

2016-02-01

The present study investigated the role of endothelial nitric oxide synthase (eNOS) enzyme in the development of left ventricular hypertrophy (LVH) in Wistar-Kyoto rats. The effect of L-arginine administration on cardiac structure, arterial stiffness, renal and systemic hemodynamic parameters was studied and the change in expression of eNOS and cystathione γ lyase (CSE) in the myocardium of LVH rats was evaluated. LVH was induced using isoprenaline (5 mg/kg, S.C.) and caffeine (62 mg/L in drinking water) for 14 days. Following to that, L-arginine (1.25 g/L in drinking water) was given for 5 weeks as a donor of NO. eNOS and CSE gene expressions were down regulated in the LVH group by about 35% and 67% respectively when compared to control. However, in the LVH group treated with L-arginine there was up regulation of eNOS by almost 27% and down regulation in CSE by 24% when compared to control (all P < 0.05). Heart index and H2S plasma levels were reduced by almost 53% in the L-arginine treated LVH group compared to the control (all P < 0.05). Mean arterial pressure, heart rate and pulse wave velocity were reduced while renal blood perfusion increased in L-arginine treated LVH rats compared to their untreated counterparts (all P < 0.05). The enhanced expression of eNOS in L-arginine treated LVH rats resulted in the amelioration of oxidative and haemodynamic parameters suggesting that NO system is an important therapeutic target in cardiac and LV hypertrophies.

Test- and behavior-specific genetic factors affect WKY hypoactivity in tests of emotionality.

PubMed

Baum, Amber E; Solberg, Leah C; Churchill, Gary A; Ahmadiyeh, Nasim; Takahashi, Joseph S; Redei, Eva E

2006-05-15

Inbred Wistar-Kyoto rats consistently display hypoactivity in tests of emotional behavior. We used them to test the hypothesis that the genetic factors underlying the behavioral decision-making process will vary in different environmental contexts. The contexts used were the open-field test (OFT), a novel environment with no explicit threats present, and the defensive-burying test (DB), a habituated environment into which a threat has been introduced. Rearing, a voluntary behavior was measured in both tests, and our study was the first to look for genetic loci affecting grooming, a relatively automatic, stress-responsive stereotyped behavior. Quantitative trait locus analysis was performed on a population of 486 F2 animals bred from reciprocal inter-crosses. The genetic architectures of DB and OFT rearing, and of DB and OFT grooming, were compared. There were no common loci affecting grooming behavior in both tests. These different contexts produced the stereotyped behavior via different pathways, and genetic factors seem to influence the decision-making pathways and not the expression of the behavior. Three loci were found that affected rearing behavior in both tests. However, in both contexts, other loci had greater effects on the behavior. Our results imply that environmental context's effects on decision-making vary depending on the category of behavior.

Metabolic profiling of rat hair and screening biomarkers using ultra performance liquid chromatography with electrospray ionization time-of-flight mass spectrometry.

PubMed

Inagaki, Shinsuke; Noda, Takumi; Min, Jun Zhe; Toyo'oka, Toshimasa

2007-12-28

An exhaustive analysis of metabolites in hair samples has been performed for the first time using ultra performance liquid chromatography with electrospray ionization time-of-flight mass spectrometry (UPLC-ESI-TOF-MS). The hair samples were collected from spontaneously hypertensive model rats (SHR/Izm), stroke-prone SHR (SHRSP/Izm) and Wistar Kyoto (WKY/Izm) rats, and were analyzed by UPLC-ESI-TOF-MS; a multivariate statistical analysis method, such as the principal component analysis (PCA), was then used for screening the biomarkers. From the samples derived from the group of SHRSP/Izm at weeks 10, 18, 26 and 34, we successfully detected a potential biomarker of stroke, which existed at much higher concentrations as compared with that in the other groups. However, a significant difference could not be found at weeks less than 7 before the rats were subjected to stroke and hypertension. In addition, the present method was applicable to screening not only the disease markers, but also the markers related to aging. The method utilizing hair samples is expected to be quite useful for screening biomarkers of many other diseases, and not limited to stroke and hypertension.

Premature hippocampus-dependent memory decline in middle-aged females of a genetic rat model of depression.

PubMed

Lim, Patrick H; Wert, Stephanie L; Tunc-Ozcan, Elif; Marr, Robert; Ferreira, Adriana; Redei, Eva E

2018-02-25

Aging and major depressive disorder are risk factors for dementia, including Alzheimer's Disease (AD), but the mechanism(s) linking depression and dementia are not known. Both AD and depression show greater prevalence in women. We began to investigate this connection using females of the genetic model of depression, the inbred Wistar Kyoto More Immobile (WMI) rat. These rats consistently display depression-like behavior compared to the genetically close control, the Wistar Kyoto Less Immobile (WLI) strain. Hippocampus-dependent contextual fear memory did not differ between young WLI and WMI females, but, by middle-age, female WMIs showed memory deficits compared to same age WLIs. This deficit, measured as duration of freezing in the fear provoking-context was not related to activity differences between the strains prior to fear conditioning. Hippocampal expression of AD-related genes, such as amyloid precursor protein, amyloid beta 42, beta secretase, synucleins, total and dephosphorylated tau, and synaptophysin, did not differ between WLIs and WMIs in either age group. However, hippocampal transcript levels of catalase (Cat) and hippocampal and frontal cortex expression of insulin-like growth factor 2 (Igf2) and Igf2 receptor (Igf2r) paralleled fear memory differences between middle-aged WLIs and WMIs. This data suggests that chronic depression-like behavior that is present in this genetic model is a risk factor for early spatial memory decline in females. The molecular mechanisms of this early memory decline likely involve the interaction of aging processes with the genetic components responsible for the depression-like behavior in this model. Copyright © 2018 Elsevier B.V. All rights reserved.

Impulsive choice behavior in four strains of rats: Evaluation of possible models of Attention Deficit/Hyperactivity Disorder

PubMed Central

Garcia, Ana; Kirkpatrick, Kimberly

2012-01-01

Several studies have examined impulsive choice behavior in spontaneously hypertensive rats (SHRs) as a possible pre-clinical model for Attention-Deficit/Hyperactivity Disorder (ADHD). However, this strain was not specifically selected for the traits of ADHD and as a result their appropriateness as a model has been questioned. The present study investigated whether SHRs would exhibit impulsive behavior in comparison to their control strain, Wistar Kyoto (WKY) rats. In addition, we evaluated a strain that has previously shown high levels of impulsive choice, the Lewis (LEW) rats and compared them with their source strain, Wistar (WIS) rats. In the first phase, rats could choose between a Smaller-sooner (SS) reward of 1 pellet after 10 s and a Larger-later (LL) reward of 2 pellets after 30 s. Subsequently, the rats were exposed to increases in LL reward magnitude and SS delay. These manipulations were designed to assess sensitivity to magnitude and delay within the choice task to parse out possible differences in using the strains as models of specific deficits associated with ADHD. The SHR and WKY strains did not differ in their choice behavior under either delay or magnitude manipulations. In comparison to WIS, LEW showed deficits in choice behavior in the delay manipulation, and to a lesser extent in the magnitude manipulation. An examination of individual differences indicated that the SHR strain may not be sufficiently homogeneous in their impulsive choice behavior to be considered as a viable model for impulse control disorders such as ADHD. The LEW strain may be worthy of further consideration for their suitability as an animal model. PMID:23085479

Effects of methylphenidate on attentional set-shifting in a genetic model of attention-deficit/hyperactivity disorder

PubMed Central

2012-01-01

Background Although deficits of attentional set-shifting have been reported in individuals with attention deficit/hyperactivity disorder (ADHD), it is rarely examined in animal models. Methods This study compared spontaneously hypertensive rats (SHRs; a genetic animal model of ADHD) and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats (normoactive control strains), on attentional set-shifting task (ASST) performance. Furthermore, the dose-effects of methylphenidate (MPH) on attentional set-shifting of SHR were investigated. In experiment 1, ASST procedures were conducted in SHR, WKY and SD rats of 8 each at the age of 5 weeks. Mean latencies at the initial phase, error types and numbers, and trials to criteria at each stage were recorded. In experiment 2, 24 SHR rats were randomly assigned to 3 groups of 8 each-- MPH-L (lower dose), MPH-H (higher dose), and SHR-vehicle groups. From 3 weeks, they were administered 2.5 mg/kg or 5 mg/kg MPH or saline respectively for 14 consecutive days. All rats were tested in the ASST at the age of 5 weeks. Results The SHRs generally exhibited poorer performance on ASST than the control WKY and SD rats. Significant strain effects on mean latency [F (2, 21) = 639.636, p < 0.001] and trials to criterion [F (2, 21) = 114.118, p < 0.001] were observed. The SHRs were found to have more perseverative and regressive errors than the control strains (p < 0.001). After MPH treatment, the two MPH treated groups exhibited significantly longer latency and fewer trials to reach criterion than the SHR-vehicle group and the MPH-L group exhibited fewer trials to reach criterion in more stages compared with the MPH-H group. Significant main effects of treatment [F (2, 21) = 52.174, p < 0.001] and error subtype [F (2, 42) = 221.635, p < 0.01] were found. Conclusions The SHR may be impaired in discrimination learning, reversal learning and attentional set-shifting. Our study provides evidence that MPH may improve the SHR's performance on attentional set

Antihypertensive effects of androgens in conscious, spontaneously hypertensive rats.

PubMed

Perusquía, Mercedes; Herrera, Nieves; Ferrer, Mercedes; Stallone, John N

2017-03-01

Androgens are vasoactive steroids that induce acute vasodilation in a number of isolated vascular beds from different species, but the effects of these hormones on systemic blood pressure (BP) have been studied little. Although it has been reported that androgens exert systemic hypotensive effects through peripheral vasodilation in normotensive rats, there have not been any reports of systemic hypotensive effects of androgens in animals with hypertension. This study was designed to evaluate the acute effects of testosterone (TES) and its 5-reduced metabolites on systemic BP in hypertensive rats and to test the hypothesis that hypotestosteronemia may be involved in the pathogenesis of hypertension. Chronic, indwelling catheters were implanted in carotid artery and jugular vein of 18-21-week-old male spontaneously hypertensive rats (SHR) and normotensive-control Wistar-Kyoto (WKY) rats, for BP recording and drug administration, respectively. Bolus injections of TES, 5α- or 5β-dihydrotestosterone (5α- and 5β-DHT), were administrated cumulatively to conscious rats at doses of 0.1-100μmolkg -1 min -1 . 5β-DHT was also administrated during the pressor effect of Bay K 8644, an L-type voltage-operated Ca 2+ channel (L-VOCC) agonist. In separate experiments, BP of orchidectomized normotensive male WKY and Wistar rats, with or without androgen-replacement therapy, was evaluated weekly for 10 weeks by tail-cuff plethysmography. TES and its metabolites reduced BP in a dose-dependent manner, while heart rate was reduced with some androgens at the highest doses. The hypotensive effects of androgens were markedly greater in SHR, with a rank order potency of: 5β-DHT>TES>5α-DHT. 5β-DHT, the most potent antihypertensive androgen, abolished the pressor response to Bay K 8644 in SHR. TES deprivation by orchidectomy increased BP in normotensive WKY and Wistar rats, but this hypertension was prevented by TES replacement therapy. BP responses to androgens are androgen structure

Febuxostat, a novel xanthine oxidoreductase inhibitor, improves hypertension and endothelial dysfunction in spontaneously hypertensive rats.

PubMed

Shirakura, Takashi; Nomura, Johji; Matsui, Chieko; Kobayashi, Tsunefumi; Tamura, Mizuho; Masuzaki, Hiroaki

2016-08-01

Xanthine oxidase (XO) is an enzyme responsible for the production of uric acid. XO produces considerable amount of oxidative stress throughout the body. To date, however, its pathophysiologic role in hypertension and endothelial dysfunction still remains controversial. To explore the possible involvement of XO-derived oxidative stress in the pathophysiology of vascular dysfunction, by use of a selective XO inhibitor, febuxostat, we investigated the impact of pharmacological inhibition of XO on hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats (SHRs). Sixteen-week-old SHR and normotensive Wistar-Kyoto (WKY) rats were treated with tap water (control) or water containing febuxostat (3 mg/kg/day) for 6 weeks. Systolic blood pressure (SBP) in febuxostat-treated SHR (220 ± 3 mmHg) was significantly (P < 0.05) decreased compared with the control SHR (236 ± 4 mmHg) while SBP in febuxostat-treated WKY was constant. Acetylcholine-induced endothelium-dependent relaxation in aortas from febuxostat-treated SHR was significantly (P < 0.05) improved compared with the control SHR, whereas relaxation in response to sodium nitroprusside was not changed. Vascular XO activity and tissue nitrotyrosine level, a representative indicator of local oxidative stress, were considerably elevated in the control SHR compared with the control WKY, and this increment was abolished by febuxostat. Our results suggest that exaggerated XO activity and resultant increase in oxidative stress in this experimental model contribute to the hypertension and endothelial dysfunction, thereby supporting a notion that pharmacological inhibition of XO is valuable not only for hyperuricemia but also for treating hypertension and related endothelial dysfunction in human clinics.

Lentil consumption reduces resistance artery remodeling and restores arterial compliance in the spontaneously hypertensive rats.

PubMed

Hanson, Matthew G; Taylor, Carla G; Wu, Yinghong; Anderson, Hope D; Zahradka, Peter

2016-11-01

We previously established that lentils were able to significantly attenuate the development of hypertension in spontaneously hypertensive rats (SHRs), but the mechanism was not investigated. The current study was therefore designed to examine the effect of lentils on arterial function in relation to arterial stiffness, lipid biochemistry and activation of select aortic proteins. Seventeen-week-old male SHRs were randomly assigned to groups (n=10/group) fed (a) 30% w/w green lentils, (b) 30% red lentils, (c) 30% mixed lentils (red and green) or (d) no lentils for 8 weeks. Normotensive Wistar Kyoto (WKY) groups (n=10/group) received either the mixed lentil or no lentil diet. Blood pressure, pulse wave velocity and serum lipids were measured at baseline and 8 weeks, while pressure myography, arterial morphology and aortic proteins were measured after termination. There were no dietary-related changes in pulse wave velocity or blood pressure for any SHR or WKY group. Low-density lipoprotein cholesterol and high-density lipoprotein cholesterol were significantly lower in only SHR red lentil and WKY mixed lentil groups compared to their controls. The lentil diets reduced the media:lumen ratio of SHRs relative to control-fed SHRs but had no effect on WKYs. Both red and green lentils reduced arterial stiffness of SHRs but not WKYs. SHR lentil groups showed lower aortic p38 mitogen-activated protein kinase (p38MAPK) phosphorylation, thus implying that p38MAPK activation is suppressed with lentil feeding. Lentil-based diets suppress pathological vascular remodeling in SHRs, while green lentils maintain the vascular function of SHRs similar to normotensive WKYs despite the presence of high blood pressure. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Valsartan on Cerebellar Adrenomedullin System Dysregulation During Hypertension.

PubMed

Figueira, Leticia; Israel, Anita

2017-02-01

Adrenomedullin (AM) and its receptors components, calcitonin-receptor-like receptor (CRLR), and receptor activity-modifying protein (RAMP1, RAMP2, and RAMP3) are expressed in cerebellum. Cerebellar AM, AM binding sites and receptor components are altered during hypertension, suggesting a role for cerebellar AM in blood pressure regulation. Thus, we assessed the effect of valsartan, on AM and its receptor components expression in the cerebellar vermis of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Additionally, we evaluated AM action on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity, and thiobarbituric acid reactive substances (TBARS) production in cerebellar vermis. Animals were treated with valsartan or vehicle for 11 days. Rats were sacrificed by decapitation; cerebellar vermis was dissected; and AM, CRLR, RAMP1, RAMP2, and RAMP3 expression was quantified by Western blot analysis. CAT, SOD, and GPx activity was determined spectrophotometrically and blood pressure by non-invasive plethysmography. We demonstrate that AM and RAMP2 expression was lower in cerebellum of SHR rats, while CRLR, RAMP1, and RAMP3 expression was higher than those of WKY rats. AM reduced cerebellar CAT, SOD, GPx activities, and TBARS production in WKY rats, but not in SHR rats. Valsartan reduced blood pressure and reversed the altered expression of AM and its receptors components, as well the loss of AM capacity to reduce antioxidant enzyme activity and TBARS production in SHR rats. These findings demonstrate that valsartan is able to reverse the dysregulation of cerebellar adrenomedullinergic system; and they suggest that altered AM system in the cerebellum could represent the primary abnormality leading to hypertension.

Application of ET-Kyoto solution in clinical lung transplantation.

PubMed

Omasa, Mitsugu; Hasegawa, Seiki; Bando, Toru; Hanaoka, Nobuharu; Yoshimura, Takashi; Nakamura, Takayuki; Wada, Hiromi

2004-01-01

We have developed a new organ preservation solution called extracellular-type trehalose-containing Kyoto (ET-Kyoto) solution. ET-Kyoto solution has been applied in clinical lung transplantation. The patient was a 49-year-old woman with diffuse panbronchiolitis. She underwent bilateral lobar lung transplantation from living donors. Each lobe was flushed with ET-Kyoto solution. After reperfusion, PaO(2) with inhalation of 100% oxygen was more than 500 Torr. Posttransplantation course was uneventful. Despite the relatively short ischemic time of this case report, ET-Kyoto solution may be feasible and safely applied in clinical lung transplantation.

Possible mechanism of the potent vasoconstrictor actions of ryanodine on femoral arteries from spontaneously hypertensive rats.

PubMed Central

Asano, M.; Kuwako, M.; Nomura, Y.; Ito, K. M.; Ito, K.; Uyama, Y.; Imaizumi, Y.; Watanabe, M.

1996-01-01

1. The Ca2+ buffering function of sarcoplasmic reticulum (SR) in the resting state of arteries from spontaneously hypertensive rats (SHR) was examined. Differences in the effects of ryanodine that removes the function of SR, on tension and cellular Ca2+ level were assessed in endothelium-denuded strips of femoral arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY). 2. The addition of ryanodine to the resting strips caused a concentration-dependent contraction in SHR. This contraction was extremely small in WKY. In the presence of 10(-5) M ryanodine, caffeine (20 mM) failed to cause a further contraction in SHR, but it caused a small contraction in WKY. After washout of the strips with a Krebs solution, the resting tone was greatly elevated in SHR when compared with WKY. 3. The elevated resting tone in SHR strips was abolished by 10(-7) M nifedipine. The ryanodine-induced contraction was also abolished by 10(-7) M nifedipine. Nifedipine itself caused a relaxation from the resting tone of SHR strips, suggesting the maintenance of myogenic tone. 4. In strips preloaded with fura-PE3, the addition of 10(-5) M ryanodine caused a large and moderate elevation of cytosolic Ca2+ level ([Ca2+]i) in SHR and WKY, respectively. After washout, the resting [Ca2+]i was greatly elevated in SHR. The ryanodine-induced elevation of [Ca2+]i was decreased by 5 x 10(-6) M verapamil in SHR. Verapamil itself caused a decrease in resting [Ca2+]i which was significantly greater in SHR than in WKY, and caused a relaxation only in SHR. 5. The resting Ca2+ influx in arteries measured by a 5 min incubation with 45Ca was significantly increased in SHR when compared with WKY. The resting Ca2+ influx was not increased by 10(-5) M ryanodine in both SHR and WKY. The net cellular Ca2+ uptake in arteries measured by a 30 min incubation with 45Ca was decreased by 10(-5) M ryanodine in both strains. 6. The resting Ca2+ influx was decreased by 10(-7) M nifedipine in the SHR artery, but

The probiotic Bifidobacterium infantis 35624 displays visceral antinociceptive effects in the rat.

PubMed

McKernan, D P; Fitzgerald, P; Dinan, T G; Cryan, J F

2010-09-01

Irritable bowel syndrome (IBS) is characterized by recurrent abdominal pain and altering bowel habit with a high percentage of patients displaying comorbid anxiety. Growing clinical and preclinical evidence suggests that probiotic agents may restore the altered brain-gut communication in IBS. In this study, we evaluated the efficacy of repeated treatment with three different probiotics in reducing visceral pain in visceral normosensitive (Sprague-Dawley [SD]) and visceral hypersensitive (Wistar-Kyoto [WKY]) rat strains. Following 14 days oral gavage of Lactobacillus salivarius UCC118, Bifidobacterium infantis 35624, or Bifidobacterium breve UCC2003 both SD and WKY rats were exposed to a novel stress, the open field arena and their behavior was recorded. Subsequently, the effects of probiotics on visceral nociceptive responses were analyzed by recording pain behaviors during colorectal distension (CRD). It was found that there was a difference in the open field behavior between strains but none of the probiotic treatment altered behavior within each strain. Interestingly, the probiotic B. infantis 35624 but not others tested significantly reduced CRD-induced visceral pain behaviors in both rat strains. It significantly increased the threshold pressure of the first pain behavior and also reduced the total number pain behaviors during CRD. These data confirm that probiotics such as B. infantis 35624 are effective in reducing visceral pain and may be effective in treating certain symptoms of IBS.

Telemetric ambulatory arterial stiffness index, a predictor of cardio-cerebro-vascular mortality, is associated with aortic stiffness-determining factors.

PubMed

Li, Zhi-Yong; Xu, Tian-Ying; Zhang, Sai-Long; Zhou, Xiao-Ming; Xu, Xue-Wen; Guan, Yun-Feng; Lo, Ming; Miao, Chao-Yu

2013-09-01

Ambulatory arterial stiffness index (AASI) has been proposed as a new measure of arterial stiffness for predicting cardio-cerebro-vascular morbidity and mortality. However, there has been no research on the direct relationships between AASI and arterial stiffness-determining factors. We utilized beat-to-beat intra-aortic blood pressure (BP) telemetry to characterize AASI in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). By determination of aortic structural components and analysis of their correlations with AASI, we provided the first direct evidence for the associations between AASI and arterial stiffness-determining factors including the collagen content and collagen/elastin. Ambulatory arterial stiffness index was positively correlated with pulse pressure in both WKY and SHR, less dependent on BP and BP variability than pulse pressure, and relatively stable, especially the number of BP readings not less than ~36. The correlations between AASI and aortic components were comparable for various AASI values derived from BP readings not less than ~36. Not only AASI but also BP variability and pulse pressure demonstrated a direct relationship with arterial stiffness. These findings indicate AASI may become a routine measure in human arterial stiffness assessment. It is recommended to use a cluster of parameters such as AASI, BP variability, and pulse pressure for evaluating arterial stiffness. © 2013 John Wiley & Sons Ltd.

Effects of S-1-propenylcysteine, a sulfur compound in aged garlic extract, on blood pressure and peripheral circulation in spontaneously hypertensive rats.

PubMed

Ushijima, Mitsuyasu; Takashima, Miyuki; Kunimura, Kayo; Kodera, Yukihiro; Morihara, Naoaki; Tamura, Koichi

2018-04-01

This study was designed to investigate the antihypertensive effect of S-1-propenylcysteine, a characteristic sulfur compound in aged garlic extract, using a hypertensive rat model. The blood pressure and tail blood flow of both spontaneously hypertensive rats and control Wistar Kyoto rats were measured by the tail-cuff method and the noncontact laser Doppler method, respectively, at various times after single oral administration of a test compound for 24 h. Treatment with S-1-propenylcysteine (6.5 mg/kg BW) significantly decreased the systolic blood pressure of spontaneously hypertensive rat approximately 10% at 3 h after administration, and thereafter, the systolic blood pressure gradually returned to the baseline level in 24 h. The effect of S-1-propenylcysteine was dose-dependent and was maximal at the dose of 6.5 mg/kg BW at 3 h. However, the other compounds such as S-allylcysteine and S-allylmercaptocysteine in aged garlic extract were ineffective. In addition, S-1-propenylcysteine had no effect on systolic blood pressure of control Wistar Kyoto rats. Furthermore, S-1-propenylcysteine significantly increased the blood flow at 3 h after administration at the dose of 6.5 mg/kg BW. S-1-propenylcysteine is a key constituent of aged garlic extract responsible for its antihypertensive effect, and the effect of S-1-propenylcysteine involves the improvement in peripheral circulation. © 2018 Royal Pharmaceutical Society.

Maternal separation affects dopamine transporter function in the spontaneously hypertensive rat: an in vivo electrochemical study.

PubMed

Womersley, Jacqueline S; Hsieh, Jennifer H; Kellaway, Lauriston A; Gerhardt, Greg A; Russell, Vivienne A

2011-12-01

Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR) is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR. It was hypothesized that maternal separation would alter dopamine regulation by the transporter (DAT) in ways that distinguish SHR from control rat strains. SHR and control Wistar-Kyoto (WKY) rats were subjected to maternal separation for 3 hours per day from postnatal day 2 to 14. Rats were tested for separation-induced anxiety-like behaviour followed by in vivo chronoamperometry to determine whether changes had occurred in striatal clearance of dopamine by DAT. The rate of disappearance of ejected dopamine was used as a measure of DAT function. Consistent with a model for ADHD, SHR were more active than WKY in the open field. SHR entered the inner zone more frequently and covered a significantly greater distance than WKY. Maternal separation increased the time that WKY spent in the closed arms and latency to enter the open arms of the elevated plus maze, consistent with other rat strains. Of note is that, maternal separation failed to produce anxiety-like behaviour in SHR. Analysis of the chronoamperometric data revealed that there was no difference in DAT function in the striatum of non-separated SHR and WKY. Maternal separation decreased the rate of dopamine clearance (k-1) in SHR striatum. Consistent with this observation, the dopamine clearance time (T100) was increased in SHR. These results suggest that the chronic mild stress of maternal separation impaired the function of striatal

Diesel exhaust induced pulmonary and cardiovascular impairment: The role of hypertension intervention

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kodavanti, Urmila P., E-mail: kodavanti.urmila@epa.gov; Thomas, Ronald F.; Ledbetter, Allen D.

Exposure to diesel exhaust (DE) and associated gases is linked to cardiovascular impairments; however, the susceptibility of hypertensive individuals is poorly understood. The objectives of this study were (1) to determine cardiopulmonary effects of gas-phase versus whole-DE and (2) to examine the contribution of systemic hypertension in pulmonary and cardiovascular effects. Male Wistar Kyoto (WKY) rats were treated with hydralazine to reduce blood pressure (BP) or L-NAME to increase BP. Spontaneously hypertensive (SH) rats were treated with hydralazine to reduce BP. Control and drug-pretreated rats were exposed to air, particle-filtered exhaust (gas), or whole DE (1500 μg/m{sup 3}), 4 h/daymore » for 2 days or 5 days/week for 4 weeks. Acute and 4-week gas and DE exposures increased neutrophils and γ-glutamyl transferase (γ-GT) activity in lavage fluid of WKY and SH rats. DE (4 weeks) caused pulmonary albumin leakage and inflammation in SH rats. Two-day DE increased serum fatty acid binding protein-3 (FABP-3) in WKY. Marked increases occurred in aortic mRNA after 4-week DE in SH (eNOS, TF, tPA, TNF-α, MMP-2, RAGE, and HMGB-1). Hydralazine decreased BP in SH while L-NAME tended to increase BP in WKY; however, neither changed inflammation nor BALF γ-GT. DE-induced and baseline BALF albumin leakage was reduced by hydralazine in SH rats and increased by L-NAME in WKY rats. Hydralazine pretreatment reversed DE-induced TF, tPA, TNF-α, and MMP-2 expression but not eNOS, RAGE, and HMGB-1. ET-1 was decreased by HYD. In conclusion, antihypertensive drug treatment reduces gas and DE-induced pulmonary protein leakage and expression of vascular atherogenic markers. - Highlights: ► Acute diesel exhaust exposure induces pulmonary inflammation in healthy rats. ► In hypertensive rats diesel exhaust effects are seen only after long term exposure. ► Normalizing blood pressure reverses lung protein leakage caused by diesel exhaust. ► Normalizing blood pressure reverses

Enhanced vasomotion of cerebral arterioles in spontaneously hypertensive rats

NASA Technical Reports Server (NTRS)

Lefer, D. J.; Lynch, C. D.; Lapinski, K. C.; Hutchins, P. M.

1990-01-01

Intrinsic rhythmic changes in the diameter of pial cerebral arterioles (30-70 microns) in anesthetized normotensive and hypertensive rats were assessed in vivo to determine if any significant differences exist between the two strains. All diameter measurements were analyzed using a traditional graphic analysis technique and a new frequency spectrum analysis technique known as the Prony Spectral Line Estimator. Graphic analysis of the data revealed that spontaneously hypertensive rats (SHR) possess a significantly greater fundamental frequency (5.57 +/- 0.28 cycles/min) of vasomotion compared to the control Wistar-Kyoto normotensive rats (WKY) (1.95 +/- 0.37 cycles/min). Furthermore, the SHR cerebral arterioles exhibited a significantly greater amplitude of vasomotion (10.07 +/- 0.70 microns) when compared to the WKY cerebral arterioles of the same diameter (8.10 +/- 0.70 microns). Diameter measurements processed with the Prony technique revealed that the fundamental frequency of vasomotion in SHR cerebral arterioles (6.14 +/- 0.39 cycles/min) was also significantly greater than that of the WKY cerebral arterioles (2.99 +/- 0.42 cycles/min). The mean amplitudes of vasomotion in the SHR and WKY strains obtained by the Prony analysis were found not to be statistically significant in contrast to the graphic analysis of the vasomotion amplitude of the arterioles. In addition, the Prony system was able to consistently uncover a very low frequency of vasomotion in both strains of rats that was typically less than 1 cycle/min and was not significantly different between the two strains. The amplitude of this slow frequency was also not significantly different between the two strains. The amplitude of the slow frequency of vasomotion (less than 1 cycle/min) was not different from the amplitude of the higher frequency (2-6 cycles/min) vasomotion by Prony or graphic analysis. These data suggest that a fundamental intrinsic defect exists in the spontaneously hypertensive rat

Coconut oil supplementation and physical exercise improves baroreflex sensitivity and oxidative stress in hypertensive rats.

PubMed

Alves, Naiane F B; Porpino, Suênia K P; Monteiro, Matheus M O; Gomes, Enéas R M; Braga, Valdir A

2015-04-01

The hypothesis that oral supplementation with virgin coconut oil (Cocos nucifera L.) and exercise training would improve impaired baroreflex sensitivity (BRS) and reduce oxidative stress in spontaneously hypertensive rats (SHR) was tested. Adult male SHR and Wistar Kyoto rats (WKY) were divided into 5 groups: WKY + saline (n = 8); SHR + saline (n = 8); SHR + coconut oil (2 mL·day(-1), n = 8); SHR + trained (n = 8); and SHR + trained + coconut oil (n = 8). Mean arterial pressure (MAP) was recorded and BRS was tested using phenylephrine (8 μg/kg, intravenous) and sodium nitroprusside (25 μg·kg(-1), intravenous). Oxidative stress was measured using dihydroethidium in heart and aorta. SHR + saline, SHR + coconut oil, and SHR + trained group showed higher MAP compared with WKY + saline (175 ± 6, 148 ± 6, 147 ± 7 vs. 113 ± 2 mm Hg; p < 0.05). SHR + coconut oil, SHR + trained group, and SHR + trained + coconut oil groups presented lower MAP compared with SHR + saline group (148 ± 6, 147 ± 7, 134 ± 8 vs. 175 ± 6 mm Hg; p < 0.05). Coconut oil combined with exercise training improved BRS in SHR compared with SHR + saline group (-2.47 ± 0.3 vs. -1.39 ± 0.09 beats·min(-1)·mm Hg(-1); p < 0.05). SHR + saline group showed higher superoxide levels when compared with WKY + saline (774 ± 31 vs. 634 ± 19 arbitrary units (AU), respectively; p < 0.05). SHR + trained + coconut oil group presented reduced oxidative stress compared with SHR + saline in heart (622 ± 16 vs. 774 ± 31 AU, p < 0.05). In aorta, coconut oil reduced oxidative stress in SHR compared with SHR + saline group (454 ± 33 vs. 689 ± 29 AU, p < 0.05). Oral supplementation with coconut oil combined with exercise training improved impaired BRS and reduced oxidative stress in SHR.

Contactless magnetocardiographic mapping in anesthetized Wistar rats: evidence of age-related changes of cardiac electrical activity.

PubMed

Brisinda, Donatella; Caristo, Maria Emiliana; Fenici, Riccardo

2006-07-01

Magnetocardiography (MCG) is the recording of the magnetic field (MF) generated by cardiac electrophysiological activity. Because it is a contactless method, MCG is ideal for noninvasive cardiac mapping of small experimental animals. The aim of this study was to assess age-related changes of cardiac intervals and ventricular repolarization (VR) maps in intact rats by means of MCG mapping. Twenty-four adult Wistar rats (12 male and 12 female) were studied, under anesthesia, with the same unshielded 36-channel MCG instrumentation used for clinical recordings. Two sets of measurements were obtained from each animal: 1) at 5 mo of age (297.5 +/- 21 g body wt) and 2) at 14 mo of age (516.8 +/- 180 g body wt). RR and PR intervals, QRS segment, and QTpeak, QTend, JTpeak, JTend, and Tpeak-end were measured from MCG waveforms. MCG imaging was automatically obtained as MF maps and as inverse localization of cardiac sources with equivalent current dipole and effective magnetic dipole models. After 300 s of continuous recording were averaged, the signal-to-noise ratio was adequate for study of atrial and ventricular MF maps and for three-dimensional localization of the underlying cardiac sources. Clear-cut age-related differences in VR duration were demonstrated by significantly longer QTend, JTend, and Tpeak-end in older Wistar rats. Reproducible multisite noninvasive cardiac mapping of anesthetized rats is simpler with MCG methodology than with ECG recording. In addition, MCG mapping provides new information based on quantitative analysis of MF and equivalent sources. In this study, statistically significant age-dependent variations in VR intervals were found.

Association between gastric cancer and the Kyoto classification of gastritis.

PubMed

Shichijo, Satoki; Hirata, Yoshihiro; Niikura, Ryota; Hayakawa, Yoku; Yamada, Atsuo; Koike, Kazuhiko

2017-09-01

Histological gastritis is associated with gastric cancer, but its diagnosis requires biopsy. Many classifications of endoscopic gastritis are available, but not all are useful for risk stratification of gastric cancer. The Kyoto Classification of Gastritis was proposed at the 85th Congress of the Japan Gastroenterological Endoscopy Society. This cross-sectional study evaluated the usefulness of the Kyoto Classification of Gastritis for risk stratification of gastric cancer. From August 2013 to September 2014, esophagogastroduodenoscopy was performed and the gastric findings evaluated according to the Kyoto Classification of Gastritis in a total of 4062 patients. The following five endoscopic findings were selected based on previous reports: atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness. A total of 3392 patients (1746 [51%] men and 1646 [49%] women) were analyzed. Among them, 107 gastric cancers were diagnosed. Atrophy was found in 2585 (78%) and intestinal metaplasia in 924 (27%). Enlarged folds, nodularity, and diffuse redness were found in 197 (5.8%), 22 (0.6%), and 573 (17%), respectively. In univariate analyses, the severity of atrophy, intestinal metaplasia, diffuse redness, age, and male sex were associated with gastric cancer. In a multivariate analysis, atrophy and male sex were found to be independent risk factors. Younger age and severe atrophy were determined to be associated with diffuse-type gastric cancer. Endoscopic detection of atrophy was associated with the risk of gastric cancer. Thus, patients with severe atrophy should be examined carefully and may require intensive follow-up. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Aging process alters hippocampal and cortical secretase activities of Wistar rats.

PubMed

Bertoldi, Karine; Cechinel, Laura Reck; Schallenberger, Bruna; Meireles, Louisiana; Basso, Carla; Lovatel, Gisele Agustini; Bernardi, Lisiane; Lamers, Marcelo Lazzaron; Siqueira, Ionara Rodrigues

2017-01-15

A growing body of evidence has demonstrated amyloid plaques in aged brain; however, little attention has been given to amyloid precursor protein (APP) processing machinery during the healthy aging process. The amyloidogenic and non-amyloidogenic pathways, represented respectively by β- and α-secretases (BACE and TACE), are responsible for APP cleavage. Our working hypothesis is that the normal aging process could imbalance amyloidogenic and non-amyloidogenic pathways specifically BACE and TACE activities. Besides, although it has been showed that exercise can modulate secretase activities in Alzheimer Disease models the relationship between exercise effects and APP processing during healthy aging process is rarely studied. Our aim was to investigate the aging process and the exercise effects on cortical and hippocampal BACE and TACE activities and aversive memory performance. Young adult and aged Wistar rats were subjected to an exercise protocol (20min/day for 2 weeks) and to inhibitory avoidance task. Biochemical parameters were evaluated 1h and 18h after the last exercise session in order to verify transitory and delayed exercise effects. Aged rats exhibited impaired aversive memory and diminished cortical TACE activity. Moreover, an imbalance between TACE and BACE activities in favor of BACE activity was observed in aged brain. Moderate treadmill exercise was unable to alter secretase activities in any brain areas or time points evaluated. Our results suggest that aging-related aversive memory decline is partly linked to decreased cortical TACE activity. Additionally, an imbalance between secretase activities can be related to the higher vulnerability to neurodegenerative diseases induced by aging. Copyright © 2016 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thanos, P.K.

The spontaneously hypertensive rat (SHR) is a widely accepted rodent model of Attention Deficit/Hyperactivity Disorder (ADHD), and methylphenidate (MP) is a central nervous systemstimulant that has been shown to have a dose-related positive effect on attention task performance in humans with ADHD. The current study was undertaken to compare SHR to its typical control strain, Wistar-Kyoto(WKY) rats, on the performance of a Visual Stimulus Position Discrimination Task (VSPDT) as well as of the responsiveness of the two rat strains to MP treatment. The rats were initially trained on the VSPDT, in which a light cue was presented randomly at threemore » different cue-light intervals (1 s, 300 ms and 100 ms) over one of two levers, and presses on the lever corresponding to the light cue were reinforced with a food pellet. Once rats reached stable performance, the treatment phase of the study began, during which they received daily intraperitoneal (IP) injections of saline, 2 mg/kg, 5 mg/kg, and 10 mg/kg of MP in a randomized order immediately prior to being tested on the VSPDT. Baseline performance accuracy on the VSPDT did not differ between the groups. Furthermore, a striking strain dissociation was evident in the response of the two strains to treatment; VSPDT performance was substantially disrupted by the 5 and 10 mg/kg dose in the WKY rats but only mildly in the SHR rats. Response omissions were also increased only in WKY rats. Finally, both strains had increased locomotor activity in the operant chamber following MP treatment. These findings point to an important difference in response tendency toMP in the two strains that supports a view that a critical difference between these strains may suggest neurochemical and neuroadaptive differences associated with the behavioral impairments of ADHD.« less

Attenuation and recovery of brain stem autoregulation in spontaneously hypertensive rats.

PubMed

Toyoda, K; Fujii, K; Ibayashi, S; Kitazono, T; Nagao, T; Takaba, H; Fujishima, M

1998-03-01

Cerebral large arteries dilate actively around the lower limits of CBF autoregulation, mediated at least partly by nitric oxide, and maintain CBF during severe hypotension. We tested the hypothesis that this autoregulatory response of large arteries, as well as the response of arterioles, is altered in spontaneously hypertensive rats (SHR) and that the altered response reverts to normal during long-term antihypertensive treatment with cilazapril, an angiotensin-converting enzyme inhibitor. In anesthetized 6- to 7-month-old normotensive Wistar-Kyoto rats (WKY), 4- and 6- to 7-month-old SHR without antihypertensive treatment, and 6- to 7-month-old SHR treated with cilazapril for 10 weeks, local CBF to the brain stem was determined with laser-Doppler flowmetry and diameters of the basilar artery and its branches were measured through a cranial window during stepwise hemorrhagic hypotension. The lower limit of CBF autoregulation shifted upward in untreated SHR to 90 to 105 mm Hg from 30 to 45 mm Hg in WKY, and it reverted to 30 to 45 mm Hg in treated SHR. In response to severe hypotension, the basilar artery dilated by 21 +/- 6% (mean +/- SD) of the baseline internal diameter in WKY. The vasodilation was impaired in untreated SHR (10 +/- 8% in 4-mo-old SHR and 4 +/- 5% in 6- to 7-month-old SHR), and was restored to 22 +/- 10% by treatment with cilazapril (P < 0.005). Dilator responses of branch arterioles to hypotension showed similar attenuation and recovery as that of the basilar artery. The data indicate that chronic hypertension impairs the autoregulatory dilation of the basilar artery as well as branch arterioles and that antihypertensive treatment with cilazapril restores the diminished dilation toward normal.

Combination of the angiotensin-converting enzyme inhibitor perindopril and the diuretic indapamide activate postnatal vasculogenesis in spontaneously hypertensive rats.

PubMed

You, Dong; Cochain, Clément; Loinard, Céline; Vilar, José; Mees, Barend; Duriez, Micheline; Lévy, Bernard I; Silvestre, Jean-Sébastien

2008-06-01

Cardiovascular risk factors are associated with reduction in both the number and function of vascular progenitor cells. We hypothesized that 1) hypertension abrogates postnatal vasculogenesis, and 2) antihypertensive treatment based on the combination of perindopril (angiotensin-converting enzyme inhibitor) and indapamide (diuretic) may counteract hypertension-induced alteration in progenitor cell-related effects. Postischemic neovascularization was significantly lower in untreated spontaneously hypertensive rats (SHRs) compared with Wistar Kyoto (WKY) rats (p < 0.05). Treatment of SHRs with perindopril and the combination of perindopril/indapamide reduced the blood pressure levels and normalized vessel growth in ischemic area. Cotreatment with perindopril and indapamide increased vascular endothelial growth factor and endothelial nitric-oxide synthase protein contents, two key proangiogenic factors. It is interesting to note that 14 days after bone marrow mononuclear cell (BM-MNC) transplantation, revascularization was significantly lower in ischemic SHRs receiving BM-MNCs isolated from SHRs compared with those receiving BM-MNCs isolated from WKY rats (p < 0.05). Alteration in proangiogenic potential of SHR BM-MNCs was probably related to the reduction in their ability to differentiate into endothelial progenitor cells in vitro. Furthermore, the number of circulating endothelial progenitor cells (EPCs) was reduced by 3.1-fold in SHRs compared with WKY rats (p < 0.001). Treatments with perindopril or perindopril/indapamide restored the ability of BM-MNCs to differentiate in vitro into EPCs, increased the number of circulating EPCs, and re-established BM-MNC proangiogenic effects. Therefore, hypertension is associated with a decrease in the number of circulating progenitor cells and in the BM-MNC proangiogenic potential, probably leading to vascular complications in this setting. The combination of perindopril and indapamide counteracts hypertension

Perivascular radiofrequency renal denervation lowers blood pressure and ameliorates cardiorenal fibrosis in spontaneously hypertensive rats

PubMed Central

Zhang, Yan; Su, Linan; Zhang, Yunrong; Wang, Qiang; Yang, Dachun; Li, De; Yang, Yongjian; Ma, Shuangtao

2017-01-01

Background Catheter-based renal denervation (RDN) is a promising approach to treat hypertension, but innervation patterns limit the response to endovascular RDN and the post-procedural renal artery narrowing or stenosis questions the endovascular ablation strategy. This study was performed to investigate the anti-hypertensive and target organ protective effects of perivascular RDN in spontaneously hypertensive rats (SHR). Methods SHR and normotensive Wistar-Kyoto (WKY) rats were divided into sham group (n = 10), radiofrequency ablation group (n = 20) in which rats received bilateral perivascular ablation with radiofrequency energy (2 watts), and chemical (10% phenol in 95% ethanol) ablation group (n = 12). The tail-cuff blood pressure was measured before the ablation and on day 14 and day 28 after the procedure. The plasma levels of creatinine, urea nitrogen, and catecholamines, urinary excretion of electrolytes and protein, and myocardial and glomerular fibrosis were analyzed and compared among the groups on day 28 after the procedure. Results We identified that 2-watt is the optimal radiofrequency power for perivascular RDN in rats. Perivascular radiofrequency and chemical ablation achieved roughly comparable blood pressure reduction in SHR but not in WKY on day 14 and day 28 following the procedure. Radiofrequency-mediated ablation substantially destroyed the renal nerves surrounding the renal arteries of both SHR and WKY without damaging the renal arteries and diminished the expression of tyrosine hydroxylase, the enzyme marker for postganglionic sympathetic nerves. Additionally, perivascular radiofrequency ablation also decreased the plasma catecholamines of SHR. Interestingly, both radiofrequency and chemical ablation decreased the myocardial and glomerular fibrosis of SHR, while neither increased the plasma creatinine and blood urea nitrogen nor affected the urinary excretion of electrolytes and protein when compared to sham group. Conclusions Radiofrequency

Grape pomace extract induced beige cells in white adipose tissue from rats and in 3T3-L1 adipocytes.

PubMed

Rodriguez Lanzi, Cecilia; Perdicaro, Diahann Jeanette; Landa, María Silvina; Fontana, Ariel; Antoniolli, Andrea; Miatello, Roberto Miguel; Oteiza, Patricia Isabel; Vazquez Prieto, Marcela Alejandra

2018-06-01

This study investigated the effects of a grape pomace extract (GPE) rich in phenolic compounds on brown-like adipocyte induction and adiposity in spontaneously hypertensive (SHR) and control normotensive Wistar-Kyoto (WKY) rats fed a high-fat diet (HFD). HFD consumption for 10 weeks significantly increased epididymal white adipose tissue (eWAT) in WKY but not in SHR rats. Supplementation with GPE (300 mg/kg body weight/day) reduced adipocyte diameter and increased levels of proteins that participate in adipogenesis and angiogenesis, i.e., peroxisome-proliferator activated receptor gamma (PPARγ), vascular endothelial grow factor-A (VEGF-A) and its receptor 2 (VEGF-R2), and partially increased the uncoupling protein 1 (UCP-1) in WKY. In both strains, GPE attenuated adipose inflammation. In eWAT from SHR, GPE increased the expression of proteins involved in adipose tissue "browning," i.e., PPARγ-coactivator-1α (PGC-1α), PPARγ, PR domain containing 16 (PRDM16) and UCP-1. In primary cultures of SHR adipocytes, GPE-induced UCP-1 up-regulation was dependent on p38 and ERK activation. Accordingly, in 3T3-L1 adipocytes treated with palmitate, the addition of GPE (30 μM) activated the β-adrenergic signaling cascade (PKA, AMPK, p38, ERK). This led to the associated up-regulation of proteins involved in mitochondrial biogenesis (PGC-1α, PPARγ, PRDM16 and UCP-1) and fatty acid oxidation (ATGL). These effects were similar to those exerted by (-)-epicatechin and quercetin, major phenolic compounds in GPE. Overall, in HFD-fed rats, supplementation with GPE promoted brown-like cell formation in eWAT and diminished adipose dysfunction. Thus, winemaking residues, rich in bioactive compounds, could be useful to mitigate the adverse effects of HFD-induced adipose dysfunction. Copyright © 2018 Elsevier Inc. All rights reserved.

Perivascular radiofrequency renal denervation lowers blood pressure and ameliorates cardiorenal fibrosis in spontaneously hypertensive rats.

PubMed

Wei, Shujie; Li, Dan; Zhang, Yan; Su, Linan; Zhang, Yunrong; Wang, Qiang; Yang, Dachun; Li, De; Yang, Yongjian; Ma, Shuangtao

2017-01-01

Catheter-based renal denervation (RDN) is a promising approach to treat hypertension, but innervation patterns limit the response to endovascular RDN and the post-procedural renal artery narrowing or stenosis questions the endovascular ablation strategy. This study was performed to investigate the anti-hypertensive and target organ protective effects of perivascular RDN in spontaneously hypertensive rats (SHR). SHR and normotensive Wistar-Kyoto (WKY) rats were divided into sham group (n = 10), radiofrequency ablation group (n = 20) in which rats received bilateral perivascular ablation with radiofrequency energy (2 watts), and chemical (10% phenol in 95% ethanol) ablation group (n = 12). The tail-cuff blood pressure was measured before the ablation and on day 14 and day 28 after the procedure. The plasma levels of creatinine, urea nitrogen, and catecholamines, urinary excretion of electrolytes and protein, and myocardial and glomerular fibrosis were analyzed and compared among the groups on day 28 after the procedure. We identified that 2-watt is the optimal radiofrequency power for perivascular RDN in rats. Perivascular radiofrequency and chemical ablation achieved roughly comparable blood pressure reduction in SHR but not in WKY on day 14 and day 28 following the procedure. Radiofrequency-mediated ablation substantially destroyed the renal nerves surrounding the renal arteries of both SHR and WKY without damaging the renal arteries and diminished the expression of tyrosine hydroxylase, the enzyme marker for postganglionic sympathetic nerves. Additionally, perivascular radiofrequency ablation also decreased the plasma catecholamines of SHR. Interestingly, both radiofrequency and chemical ablation decreased the myocardial and glomerular fibrosis of SHR, while neither increased the plasma creatinine and blood urea nitrogen nor affected the urinary excretion of electrolytes and protein when compared to sham group. Radiofrequency-mediated perivascular RDN may become a

Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters.

PubMed

Leffa, Douglas Teixeira; Bellaver, Bruna; Salvi, Artur Alban; de Oliveira, Carla; Caumo, Wolnei; Grevet, Eugenio Horacio; Fregni, Felipe; Quincozes-Santos, André; Rohde, Luis Augusto; Torres, Iraci L S

2018-04-05

Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear. We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS. Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated. TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines. TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored. Copyright © 2018 Elsevier Inc. All rights reserved.

Trace elements in lenses of normal Wistar Kyoto rats

NASA Astrophysics Data System (ADS)

Kinoshita, Akio; Gong, Huaqing; Amemiya, Tsugio; Takaya, Kenichi; Tozu, Miyako; Ohashi, Yoshiharu

2003-01-01

Chemical analysis of the element and organic substance at the site of pathological changes due to aging is one of the approaches of cataract research. Time of flight secondary ion mass spectrometry (TOF-SIMS) microscopy is expected to analyze elements and organic substances in the lens. The purpose of the present study is to compare elements and organic substances in the lenses of normal 4-month-old rats with those of normal 15-month-old rats by means of a TOF-SIMS microscope. The present study showed that the concentration of Ca and Fe was significantly higher, and that of Na and Mg was significantly lower in 15-month-old rats than that in 4-month-old rats. No changes were found in the concentration of K. The present study also showed that the equator contained more Ca, Na and Mg than the nucleus; in contrast, the Cu concentration was higher in the nucleus than in the equator. In 15-month-old rats, Mg and Vit. A in the equator and Zn in the nucleus were significantly lower than those in 4-month-old rats. TOF-SIMS microscopy could detect elemental changes in the rat lens with age, and is expected to be useful approach of cataract studies.

Scatterplot analysis of EEG slow-wave magnitude and heart rate variability: an integrative exploration of cerebral cortical and autonomic functions.

PubMed

Kuo, Terry B J; Yang, Cheryl C H

2004-06-15

To explore interactions between cerebral cortical and autonomic functions in different sleep-wake states. Active waking (AW), quiet sleep (QS), and paradoxical sleep (PS) of adult male Wistar-Kyoto rats (WKY) on their daytime sleep were compared. Ten WKY. All rats had electrodes implanted for polygraphic recordings. One week later, a 6-hour daytime sleep-wakefulness recording session was performed. A scatterplot analysis of electroencephalogram (EEG) slow-wave magnitude (0.5-4 Hz) and heart rate variability (HRV) was applied in each rat. The EEG slow-wave-RR interval scatterplot from all of the recordings revealed a propeller-like pattern. If the scatterplot was divided into AW, PS, and QS according to the corresponding EEG mean power frequency and nuchal electromyogram, the EEG slow wave-RR interval relationship became nil, negative, and positive for AW, PS, and QS, respectively. A significant negative relationship was found for EEG slow-wave and high-frequency power of HRV (HF) coupling during PS and for EEG slow wave and low-frequency power of HRV to HF ratio (LF/HF) coupling during QS. The optimal time lags for the slow wave-LF/HF relationship were different between PS and QS. Bradycardia noted in QS and PS was related to sympathetic suppression and vagal excitation, respectively. The EEG slow wave-HRV scatterplot may provide unique insights into studies of sleep, and such a relationship may delineate the sleep-state-dependent fluctuations in autonomic nervous system activity.

Atypical Microglial Response to Biodiesel Exhaust in Healthy ...

EPA Pesticide Factsheets

Accumulating evidence suggests a deleterious role for urban air pollution in central nervous system (CNS) diseases and neurodevelopmental disorders. Microglia, the resident innate immune cells and sentinels in the brain, are a common source of neuroinflammation and are implicated air pollution-induced CNS effects. While renewable energy, such as soy-based biofuel, is of increasing public interest, there is little information on how soy biofuel may affect the brain. especially in people with preexisting conditions. To address this, male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats were exposed to 100% Soy Biodiesel Exhaust (100SBE; 0, 50, 150 and 500 μg/m3) by inhalation for 4 h/day for 4 weeks (5 days/week). Ionized calcium-binding adapter molecule- 1(IBA-1) staining of microglia in the substantia nigra revealed significant changes in morphology with 100SBE exposure in rats from both genotypes where SHR were less sensitive. Aconitase activity was inhibited in the frontal cortex and cerebellum of WKY rats exposed to 100SBDE. No consistent changes occurred in pro-inflammatory cytokine expression, nitrated protein, or arginase1 expression in brain regions from either rat strain exposed to 100SBE. However, while IBA-1 mRNA expression was not modified, CX3CR1 mRNA expression was lower in the striatum of 100SBE exposed rats regardless of genotype, suggesting a downregulation of the fractalkine receptor on microglia in this br

Influence of antipsychotic agents on heart rate variability in male WKY rats: implications for cardiovascular safety.

PubMed

Wang, Ying-Chieh; Chen, Chun-Yu; Kuo, Terry B J; Lai, Ching-Jung; Yang, Cheryl C H

2012-06-01

Sudden cardiac death is higher among schizophrenic patients and is associated with parasympathetic hypoactivity. Antipsychotic agents are highly suspected to be a precipitating factor. Thus, we aimed to test if the antipsychotics haloperidol, risperidone and clozapine affect cardiac autonomic function, excluding the confounding effect of altered sleep structure by the drugs. In this study, haloperidol, risperidone and clozapine were given separately by intraperitoneal injection to male Wistar-Kyoto rats for 5 days. Electroencephalogram (EEG), electromyogram (EMG) and electrocardiographic signals were recorded at baseline and 5 days after drug treatments. Sleep scoring was based on EEG and EMG signals. Cardiac autonomic function was assessed using heart rate variability analysis. Clozapine increased heart rate and suppressed cardiac sympathetic and parasympathetic activity. Cardiac acceleration was more severe during sleep. Haloperidol tended to decrease heart rate while risperidone mildly increased heart rate; however, their effects were less obvious than those of clozapine. There was a significant drug-by-stage interaction on several heart rate variability measures. Taking this evidence as a whole, we conclude that haloperidol has a better level of cardiovascular safety than either risperidone or clozapine. Application of this approach to other psychotropic agents in the future will be a useful and helpful way to evaluate the cardiovascular safety of the various psychotropic medications that are in clinical use. Copyright © 2012 S. Karger AG, Basel.

Developing the Digital Kyoto Collection in Education and Research.

PubMed

Hill, Mark Anthony

2018-04-16

The Kyoto embryo collection was begun in 1961 by Dr. Hideo Nishimura. The collection has been continuously developed and currently contains over 44,000 human normal and abnormal specimens. Beginning online in 1997, the internet provided an opportunity to make embryos from the collection widely available for research and educational purposes (http://tiny.cc/Embryo). These embryonic development resources have been continuously published and available from that time until today. Published in Japanese as an Atlas of Embryonic Development. Published online as the Kyoto Human Embryo Visualization Project (http://atlas.cac.med.kyoto-u.ac.jp) and also as the Human Embryo Atlas (http://tiny.cc/Human_Embryo_Atlas). Published now electronically as a digital eBook (http://tiny.cc/Kyoto_Collection_eBook). This new digital format allows incorporation of whole embryo and histology manipulable images, labels, and a linked glossary. New imaging modalities of magnetic resonance imaging (MRI) and episcopic fluorescence image capture (EFIC) can also be easily displayed as animations. For research, the collection specimens and histological sections have been extensively studied and published in several hundred papers, discussed here and elsewhere in this special edition. I will also describe how the Kyoto collection will now form a major partner of a new international embryology research group, the Digital Embryology Consortium (https://human-embryology.org). The digital Kyoto collection will be made available for remote researcher access, analysis, and comparison with other collections allowing new research and educational applications. This work was presented at the 40th Anniversary Commemoration Symposium of the Congenital Anomaly Research Center, Graduate School of Medicine, Kyoto University, Japan, November, 2015. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Ocean fertilization, carbon credits and the Kyoto Protocol

NASA Astrophysics Data System (ADS)

Westley, M. B.; Gnanadesikan, A.

2008-12-01

Commercial interest in ocean fertilization as a carbon sequestration tool was excited by the December 1997 agreement of the Kyoto Protocol to the United Nations Convention on Climate Change. The Protocol commits industrialized countries to caps on net greenhouse gas emissions and allows for various flexible mechanisms to achieve these caps in the most economically efficient manner possible, including trade in carbon credits from projects that reduce emissions or enhance sinks. The carbon market was valued at 64 billion in 2007, with the bulk of the trading (50 billion) taking place in the highly regulated European Union Emission Trading Scheme, which deals primarily in emission allowances in the energy sector. A much smaller amount, worth $265 million, was traded in the largely unregulated "voluntary" market (Capoor and Ambrosi 2008). As the voluntary market grows, so do calls for its regulation, with several efforts underway to set rules and standards for the sale of voluntary carbon credits using the Kyoto Protocol as a starting point. Four US-based companies and an Australian company currently seek to develop ocean fertilization technologies for the generation of carbon credits. We review these plans through the lens of the Kyoto Protocol and its flexible mechanisms, and examine whether and how ocean fertilization could generate tradable carbon credits. We note that at present, ocean sinks are not included in the Kyoto Protocol, and that furthermore, the Kyoto Protocol only addresses sources and sinks of greenhouse gases within national boundaries, making open-ocean fertilization projects a jurisdictional challenge. We discuss the negotiating history behind the limited inclusion of land use, land use change and forestry in the Kyoto Protocol and the controversy and eventual compromise concerning methodologies for terrestrial carbon accounting. We conclude that current technologies for measuring and monitoring carbon sequestration following ocean fertilization

Alterations in lenticular proteins during ageing and selenite-induced cataractogenesis in Wistar rats

PubMed Central

Sakthivel, Muniyan; Elanchezhian, Rajan; Thomas, Philip A.

2010-01-01

Purpose To determine putative alterations in the major lenticular proteins in Wistar rats of different ages and to compare these alterations with those occurring in rats with selenite-induced cataract. Methods Lenticular transparency was determined by morphological examination using slit-lamp biomicroscopy. Alterations in lenticular protein were determined by sodium dodecyl sulfate-PAGE (SDS–PAGE) and confirmed immunologically by western blot. Results Morphological examination did not reveal observable opacities in the lenses of the rats of different age groups; however, dense nuclear opacities were noted in lenses of rats in the selenite-cataract group. Western blot assays revealed age-related changes in soluble and urea-soluble lenticular proteins. Decreased αA- and βB1-crystallins in the soluble fraction and aggregation of αA-crystallin, in addition to the degraded fragment of βB1-crystallin, in the urea-soluble fraction appeared to occur in relation to increasing age of the rats from which the lenses were taken; similarly, cytoskeletal proteins appeared to decline with increasing age. The lenses from rats in the selenite-cataract group exhibited similar changes, except that there was also high molecular weight aggregation of αA-crystallin. Conclusions The results of this study suggest that there is loss, as well as aggregation, of αA-crystallin in the aging rat lens, although there is no accompanying loss of lenticular transparency. PMID:20300567

Alterations in lenticular proteins during ageing and selenite-induced cataractogenesis in Wistar rats.

PubMed

Sakthivel, Muniyan; Elanchezhian, Rajan; Thomas, Philip A; Geraldine, Pitchairaj

2010-03-16

To determine putative alterations in the major lenticular proteins in Wistar rats of different ages and to compare these alterations with those occurring in rats with selenite-induced cataract. Lenticular transparency was determined by morphological examination using slit-lamp biomicroscopy. Alterations in lenticular protein were determined by sodium dodecyl sulfate-PAGE (SDS-PAGE) and confirmed immunologically by western blot. Morphological examination did not reveal observable opacities in the lenses of the rats of different age groups; however, dense nuclear opacities were noted in lenses of rats in the selenite-cataract group. Western blot assays revealed age-related changes in soluble and urea-soluble lenticular proteins. Decreased alphaA- and betaB1-crystallins in the soluble fraction and aggregation of alphaA-crystallin, in addition to the degraded fragment of betaB1-crystallin, in the urea-soluble fraction appeared to occur in relation to increasing age of the rats from which the lenses were taken; similarly, cytoskeletal proteins appeared to decline with increasing age. The lenses from rats in the selenite-cataract group exhibited similar changes, except that there was also high molecular weight aggregation of alphaA-crystallin. The results of this study suggest that there is loss, as well as aggregation, of alphaA-crystallin in the aging rat lens, although there is no accompanying loss of lenticular transparency.

Different responses in soleus muscle fibers of Wistar and Wistar Hannover rats to hindlimb unloading

NASA Astrophysics Data System (ADS)

Wang, Xiaodong; Kawano, Fuminori; Terada, Masahiro; Matsuoka, Yoshikazu; Shinoda, Yo; Ishihara, Akihiko; Ohira, Yoshinobu

2005-08-01

Effects of 16 days of hindlimb suspension on the characteristics of single soleus muscle fibers were compared between male Wistar and Wistar Hannover rats (5 weeks old). The greater effects of unloading were noted in Wistar Hannover rats. The unloading-related reductions of muscle weight and fiber cross-sectional area vs. the pre-suspension levels were greater than Wistar rats. The percent of fibers expressing pure type I myosin heavy chain (MHC) was decreased and that of type I+II MHC fibers was increased, the magnitudes of these changes were greater than Wistar rats. Total number of myonuclei in control situation was greater in Wistar Hannover rats, but the more numbers of myonuclei were decreased following unloading. Responses of myonuclear domain levels were similar. The numbers of both quiescent and mitotic active satellite cells in control situation were greater in Wistar rats. But the magnitude of the unloading- related decrease was identical for Wistar Hannover and Wistar rats. Although the level of heat shock protein 27 (HSP27) expression in Wistar rats was decreased by unloading, de novo appearance of HSP27 was noted in Wistar Hannover rats. It is suggested that greater responses of soleus muscle fibers of Wistar Hannover than Wistar rats may be related to the different expression of protein, although the precise mechanism is still unclear.

The characteristic of the earthquake damage in Kyoto during the historical period

NASA Astrophysics Data System (ADS)

Nishiyama, Akihito

2017-04-01

The Kyoto city is located in the northern part of the Kyoto basin, central Japan and has a history of more than 1200 years. Kyoto has long been populated area with many buildings, and the center of politics, economics and culture of Japan. Due to historical large earthquakes, the Kyoto city was severely damaged such as collapses of buildings and human casualties. In the historical period, the Kyoto city has experienced six damaging large earthquake of 976, 1185, 1449, 1596, 1662 and 1830. Among them, Kyoto has experienced three damaging large earthquakes from the end of the 16th century to the middle of the 19th century, when the urban area was being expanded. All of these earthquakes are considered to be not the earthquakes in the Kyoto basin but inland earthquakes occurred in the surrounding area. The earthquake damage in Kyoto during the historical period is strongly controlled by ground conditions and earthquakes resistance of buildings rather than distance from the estimated source fault. To better estimate seismic intensity based on building damage, it is necessary to consider the state of buildings (e.g., elapsed years since established, histories of repairs and/or reinforcements, building structures) as well as the strength of ground shakings. By considering the strength of buildings at the time of an earthquake occurrence, the seismic intensity distribution due to historical large earthquakes can be estimated with higher reliability than before. The estimated seismic intensity distribution map for such historical earthquakes can be utilized for developing the strong ground motion prediction in the Kyoto basin.

The relative age effect in soccer: a match-related perspective.

PubMed

Vaeyens, Roel; Philippaerts, Renaat M; Malina, Robert M

2005-07-01

Asymmetries in the distributions of birth dates in senior professional and youth soccer players have been interpreted as evidence for systematic discrimination against individuals born shortly before the cut-off date in assigning youth to specific age groups. This concept is known as the "relative age effect". The results of a longitudinal study of birth date distritubions of 2757 semi-professional and amateur senior soccer players in Belgium are presented. Records for competitive games were available in official statistics provided by the Royal Belgian Football Association. The chi-square statistic was used to examine differences between observed and expected birth date distributions. Regression analyses indicated a shift of bias when two different start dates were compared. Players born in the early part of the new age band (January to March) were over-represented compared with players born late in the new selection period (October to December). However, players with birthdays at the start of the old selection year (August) were still represented. In a retrospective analysis of 2138 players, variables indicative of match involvement, number of selections for matches, and time played were examined in relation to the relative age effect. The group of semi-professional and amateur senior soccer players born in the first quarter of the selected age band received more playing opportunities. Comparisons of birth date distributions (traditional approach to relative age effect) with match-related variables gave similar, though not entirely consistent, results. However, there were no differences for the mean number of selections and for playing minutes between players born at the start or the end of the selection year. Our findings suggest that match-based variables may provide a more reliable indication of the relative age effect in soccer.

Recipient-donor age matching in liver transplantation: a single-center experience.

PubMed

Pagano, D; Grosso, G; Vizzini, G; Spada, M; Cintorino, D; Malaguarnera, M; Donati, M; Mistretta, A; Gridelli, B; Gruttadauria, S

2013-09-01

The aim of this study was to investigate whether donor age was a predictor of outcomes in liver transplantation, representing an independent risk factor as well as its impact related to recipient age-matching. We analyzed prospectively collected data from 221 adult liver transplantations performed from January 2006 to September 2009. Compared with recipients who received grafts from donors <60 years old, transplantation from older donors was associated with significantly higher rates of graft rejection (9.5% vs 3.5%; P = .05) and worse graft survival (P = .021). When comparing recipient and graft survivals according to age matching, we observed significantly worse values for age-mismatched (P values .029 and .037, respectively) versus age-matched patients. After adjusting for covariates in a multivariate model, age mismatch was an independent risk factor for patient death (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.1-4.17; P = .027) and graft loss (HR 3.86, 95% CI 1.02-15.47; P = .046). The results of this study suggest to that optimized donor allocation takes into account both donor and recipient ages maximize survival of liver-transplanted patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Reflex effects on renal nerve activity characteristics in spontaneously hypertensive rats.

PubMed

DiBona, G F; Jones, S Y; Sawin, L L

1997-11-01

The effects of arterial and cardiac baroreflex activation on the discharge characteristics of renal sympathetic nerve activity were evaluated in conscious spontaneously hypertensive and Wistar-Kyoto rats. In spontaneously hypertensive rats compared with Wistar-Kyoto rats, (1) arterial baroreflex regulation of renal sympathetic nerve activity was reset to a higher arterial pressure and the gain was decreased and (2) cardiac baroreflex regulation of renal sympathetic nerve activity exhibited a lower gain. With the use of sympathetic peak detection analysis, the inhibition of integrated renal sympathetic nerve activity, which occurred during both increased arterial pressure (arterial baroreflex) and right atrial pressure (cardiac baroreflex), was due to parallel decreases in peak height with little change in peak frequency in both spontaneously hypertensive and Wistar-Kyoto rats. Arterial and cardiac baroreflex inhibition of renal sympathetic nerve activity in Wistar-Kyoto and spontaneously hypertensive rats is due to a parallel reduction in the number of active renal sympathetic nerve fibers.

Enhanced vasorelaxant effects of the endocannabinoid-like mediator, oleamide, in hypertension.

PubMed

Hopps, Jamie J; Dunn, William R; Randall, Michael D

2012-06-05

Oleamide is an endocannabinoid-like, fatty acid amide with structural similarities to anandamide. The cardiovascular effects of anandamide are enhanced in hypertension and we have now examined how hypertension affects responses to oleamide. Vasorelaxant responses to oleamide were significantly (P<0.001) enhanced in aortic rings from spontaneously hypertensive rats (SHRs), such that the maximal relaxation to oleamide was 40.3 ± 3.5%, compared to 15.7 ± 3.9% in normotensive Wistar Kyoto (WKY) controls. The augmented responses to oleamide in SHR arteries were unaffected by either inhibition of nitric oxide synthase (300 μM l-NAME) or fatty acid amide hydrolase (1 μM URB597) and independent of cannabinoid CB(1) receptors or the endothelium. The enhanced responses to oleamide were opposed by pre-treatment with capsaicin (such that R(max) was reduced to 9.8 ± 1.5%) and this occurred independently of TRPV1 receptor and sensory nerve activity, as the TRPV1 antagonist capsazepine (1-5 μM) and the cation channel inhibitor ruthenium red (10 μM) had no effect on the responses to oleamide. However, inhibition of cyclooxygenase (10 μM indomethacin) enhanced the responses in the WKY aortae, such that the responses were comparable to those in the SHR. The results suggest that the cyclooxygenase pathway has a role in modulating vasorelaxation caused by oleamide in normotensive aortae and that this is lost in hypertension, possibly as an adaptation to the increase in blood pressure. Copyright © 2012 Elsevier B.V. All rights reserved.

Novel Method to Assess Arterial Insufficiency in Rodent Hindlimb

PubMed Central

Ziegler, Matthew A.; DiStasi, Matthew R.; Miller, Steven J.; Dalsing, Michael C.; Unthank, Joseph L.

2015-01-01

Background Lack of techniques to assess maximal blood flow capacity thwarts the use of rodent models of arterial insufficiency to evaluate therapies for intermittent claudication. We evaluated femoral vein outflow (VO) in combination with stimulated muscle contraction as a potential method to assess functional hindlimb arterial reserve and therapeutic efficacy in a rodent model of subcritical limb ischemia. Materials and methods VO was measured with perivascular flow probes at rest and during stimulated calf muscle contraction in young healthy rats (Wistar Kyoto, WKY; lean Zucker, LZR) and rats with cardiovascular risk factors (Spontaneously Hypertensive, SHR; Obese Zucker, OZR) with acute and/or chronic femoral arterial occlusion. Therapeutic efficacy was assessed by administration of Ramipril or Losartan to SHR after femoral artery excision. Results VO measurement in WKY demonstrated the utility of this method to assess hindlimb perfusion at rest and during calf muscle contraction. While application to diseased models (OZR, SHR) demonstrated normal resting perfusion compared to contralateral limbs, a significant reduction in reserve capacity was uncovered with muscle stimulation. Administration of Ramipril and Losartan demonstrated significant improvement in functional arterial reserve. Conclusion The results demonstrate that this novel method to assess distal limb perfusion in small rodents with subcritical limb ischemia is sufficient to unmask perfusion deficits not apparent at rest, detect impaired compensation in diseased animal models with risk factors, and assess therapeutic efficacy. The approach provides a significant advance in methods to investigate potential mechanisms and novel therapies for subcritical limb ischemia in pre-clinical rodent models. PMID:26850199

Changes in the Brain Endocannabinoid System in Rat Models of Depression.

PubMed

Smaga, Irena; Jastrzębska, Joanna; Zaniewska, Magdalena; Bystrowska, Beata; Gawliński, Dawid; Faron-Górecka, Agata; Broniowska, Żaneta; Miszkiel, Joanna; Filip, Małgorzata

2017-04-01

A growing body of evidence implicates the endocannabinoid (eCB) system in the pathophysiology of depression. The aim of this study was to investigate the influence of changes in the eCB system, such as levels of neuromodulators, eCB synthesizing and degrading enzymes, and cannabinoid (CB) receptors, in different brain structures in animal models of depression using behavioral and biochemical analyses. Both models used, i.e., bulbectomized (OBX) and Wistar Kyoto (WKY) rats, were characterized at the behavioral level by increased immobility time. In the OBX rats, anandamide (AEA) levels were decreased in the prefrontal cortex, hippocampus, and striatum and increased in the nucleus accumbens, while 2-arachidonoylglycerol (2-AG) levels were increased in the prefrontal cortex and decreased in the nucleus accumbens with parallel changes in the expression of eCB metabolizing enzymes in several structures. It was also observed that CB 1 receptor expression decreased in the hippocampus, dorsal striatum, and nucleus accumbens, and CB 2 receptor expression decreased in the prefrontal cortex and hippocampus. In WKY rats, the levels of eCBs were reduced in the prefrontal cortex (2-AG) and dorsal striatum (AEA) and increased in the prefrontal cortex (AEA) with different changes in the expression of eCB metabolizing enzymes, while the CB 1 receptor density was increased in several brain regions. These findings suggest that dysregulation in the eCB system is implicated in the pathogenesis of depression, although neurochemical changes were linked to the particular brain structure and the factor inducing depression (surgical removal of the olfactory bulbs vs. genetic modulation).

Age-related changes in the water-soluble lens protein composition of Wistar and accelerated-senescence OXYS rats

PubMed Central

Kopylova, Lyudmila V.; Cherepanov, Ivan V.; Snytnikova, Olga A.; Rumyantseva, Yuliya V.; Kolosova, Nataliya G.; Sagdeev, Renad Z.

2011-01-01

Purpose To determine the age-related and the cataract-specific changes in the crystallin composition in lenses of accelerated-senescence OXYS (cataract model) and Wistar (control) rats. Methods The water soluble (WS) and insoluble (WIS) fractions of the lens proteins were separated; the identity and relative abundance of each crystallin in WS fraction were determined with the use of two-dimensional electrophoresis (2-DE) and Matrix-Assisted Laser Desorption Ionization – Time Of Flight (MALDI-TOF) mass spectrometry. All statistical calculations were performed using the software package Statistica 6.0 by factor dispersion analysis (ANOVA/MANOVA) and Newman-Keuls post-hoc test for comparison of group mean values. Results The WIS protein content increased significantly in the aged animal lenses; the WIS/WS ratio increases in approximately 8 times to the age of 62 weeks. The interstrain difference was insignificant in this experiment. 2-DE maps of the young rat lenses (3 weeks) showed single spots for each lens protein while in older lenses (12 and 62 weeks) each crystallin was presented by several spots. The abundance of γA-γF-crystallins in WS fraction significantly decreases with age. A significant increase in the percentage abundance was also found for α-crystallins and βB2-crystallin from 3 to 12 weeks. The major differences between Wistar and OXYS lenses are the faster decay of the content of γA-γF-crystallins in OXYS lenses, and the significant decrease of unmodified αA-crystallin abundance in old OXYS lenses. Conclusions The presented results demonstrate that the increase of the water-insoluble (WIS) protein fraction is rather age-specific than cataract-specific phenomenon. The major age-related changes in WS protein composition are the fast insolubilization of γ-crystallins, and the increase of αB- and βB2-crystallin abundance. The main interstrain differences, which could be attributed to the cataract-specific processes, are the faster decay of the

The characteristic of the building damage from historical large earthquakes in Kyoto

NASA Astrophysics Data System (ADS)

Nishiyama, Akihito

2016-04-01

The Kyoto city, which is located in the northern part of Kyoto basin in Japan, has a long history of >1,200 years since the city was initially constructed. The city has been a populated area with many buildings and the center of the politics, economy and culture in Japan for nearly 1,000 years. Some of these buildings are now subscribed as the world's cultural heritage. The Kyoto city has experienced six damaging large earthquakes during the historical period: i.e., in 976, 1185, 1449, 1596, 1662, and 1830. Among these, the last three earthquakes which caused severe damage in Kyoto occurred during the period in which the urban area had expanded. These earthquakes are considered to be inland earthquakes which occurred around the Kyoto basin. The damage distribution in Kyoto from historical large earthquakes is strongly controlled by ground condition and earthquakes resistance of buildings rather than distance from estimated source fault. Therefore, it is necessary to consider not only the strength of ground shaking but also the condition of building such as elapsed years since the construction or last repair in order to more accurately and reliably estimate seismic intensity distribution from historical earthquakes in Kyoto. The obtained seismic intensity map would be helpful for reducing and mitigating disaster from future large earthquakes.

THE EFFECT OF GREEN TEA ON OXIDATIVE DAMAGE AND TUMOUR FORMATION IN LOBUND-WISTAR RATS

PubMed Central

O'Sullivan, Jacintha; Sheridan, Juliette; Mulcahy, Hugh; Tenniswood, Martin; Morrissey, Colm

2014-01-01

A number of epidemiological studies suggest that the consumption of green tea reduces the incidence of prostate cancer. Since the major catechins present in green tea are potent anti-oxidants, we hypothesized that genetic and cellular damage induced by oxygen free radicals could be significantly reduced by potent anti-oxidants in green tea, thus reducing the cumulative genetic and cellular damage with age, and slowing or preventing tumour formation. Long-term administration of a decaffeinated green tea extract to Lobund-Wistar rats for periods up to 26 months almost halved the incidence of primary tumours in the genitourinary tract when compared to an aged-matched cohort receiving just water. We observed no inhibition of DNA adduct formation or lipid peroxidation in animals consuming green tea compared to animals consuming de-ionized water. The decrease in tumour formation was associated with an increase in 8-hydroxy-2’deoxyguanosine (8-OH-dG) and 4-hydroxynonenal (4-HNE) content (markers of DNA adduct formation and lipid peroxidation respectively) in the epithelium of the ventral prostate in aging animals. There was also an increase in 8-OH-dG expression, but no change in 4-HNE expression in the seminal vesicles of older animals. There was an age associated increase in expression of the anti-oxidant enzymes MnSOD and catalase in the epithelium of the ventral prostate of aging animals. There was also an increase in MnSOD expression, but no change in catalase expression in the seminal vesicles of older animals. These data demonstrate that consumption of green tea decreases the incidence of genitourinary tract tumours in the Lobund-Wistar rat, but has no effect on age associated DNA adduct formation and lipid peroxidation in the aging rat ventral prostate and seminal vesicles. PMID:18941371

Renal actions of atrial natriuretic peptide in spontaneously hypertensive rats: the role of nitric oxide as a key mediator.

PubMed

Elesgaray, Rosana; Caniffi, Carolina; Savignano, Lucía; Romero, Mariana; Mac Laughlin, Myriam; Arranz, Cristina; Costa, María A

2012-06-01

Atrial natriuretic peptide (ANP) is an important regulator of blood pressure (BP). One of the mechanisms whereby ANP impacts BP is by stimulation of nitric oxide (NO) production in different tissues involved in BP control. We hypothesized that ANP-stimulated NO is impaired in the kidneys of spontaneously hypertensive rats (SHR) and this contributes to the development and/or maintenance of high levels of BP. We investigated the effects of ANP on the NO system in SHR, studying the changes in renal nitric oxide synthase (NOS) activity and expression in response to peptide infusion, the signaling pathways implicated in the signaling cascade that activates NOS, and identifying the natriuretic peptide receptors (NPR), guanylyl cyclase receptors (NPR-A and NPR-B) and/or NPR-C, and NOS isoforms involved. In vivo, SHR and Wistar-Kyoto rats (WKY) were infused with saline (0.05 ml/min) or ANP (0.2 μg·kg(-1)·min(-1)). NOS activity and endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) NOS expression were measured in the renal cortex and medulla. In vitro, ANP-induced renal NOS activity was determined in the presence of iNOS and nNOS inhibitors, NPR-A/B blockers, guanine nucleotide-regulatory (G(i)) protein, and calmodulin inhibitors. Renal NOS activity was higher in SHR than in WKY. ANP increased NOS activity, but activation was lower in SHR than in WKY. ANP had no effect on expression of NOS isoforms. ANP-induced NOS activity was not modified by iNOS and nNOS inhibitors. NPR-A/B blockade blunted NOS stimulation via ANP in kidney. The renal NOS response to ANP was reduced by G(i) protein and calmodulin inhibitors. We conclude that ANP interacts with NPR-C, activating Ca-calmodulin eNOS through G(i) protein. NOS activation also involves NPR-A/B. The NOS response to ANP was diminished in kidneys of SHR. The impaired NO system response to ANP in SHR participates in the maintenance of high blood pressure.

Evidence for impulsivity in the Spontaneously Hypertensive Rat drawn from complementary response-withholding tasks

PubMed Central

Sanabria, Federico; Killeen, Peter R

2008-01-01

Background The inability to inhibit reinforced responses is a defining feature of ADHD associated with impulsivity. The Spontaneously Hypertensive Rat (SHR) has been extolled as an animal model of ADHD, but there is no clear experimental evidence of inhibition deficits in SHR. Attempts to demonstrate these deficits may have suffered from methodological and analytical limitations. Methods We provide a rationale for using two complementary response-withholding tasks to doubly dissociate impulsivity from motivational and motor processes. In the lever-holding task (LHT), continual lever depression was required for a minimum interval. Under a differential reinforcement of low rates schedule (DRL), a minimum interval was required between lever presses. Both tasks were studied using SHR and two normotensive control strains, Wistar-Kyoto (WKY) and Long Evans (LE), over an overlapping range of intervals (1 – 5 s for LHT and 5 – 60 s for DRL). Lever-holding and DRL performance was characterized as the output of a mixture of two processes, timing and iterative random responding; we call this account of response inhibition the Temporal Regulation (TR) model. In the context of TR, impulsivity was defined as a bias toward premature termination of the timed intervals. Results The TR model provided an accurate description of LHT and DRL performance. On the basis of TR parameter estimates, SHRs were more impulsive than LE rats across tasks and target times. WKY rats produced substantially shorter timed responses in the lever-holding task than in DRL, suggesting a motivational or motor deficit. The precision of timing by SHR, as measured by the variance of their timed intervals, was excellent, flouting expectations from ADHD research. Conclusion This research validates the TR model of response inhibition and supports SHR as an animal model of ADHD-related impulsivity. It indicates, however, that SHR's impulse-control deficit is not caused by imprecise timing. The use of ad hoc

Study on the cerebrovascular reserve capacity by MR perfusion weighted imaging in SHR

NASA Astrophysics Data System (ADS)

Zhou, Quan; Dong, Yang; Chen, WenLi; Lin, Xueying; Xing, Da; Huang, Li

2007-05-01

Cerebrovascular disease is one of the leading causes of death, and approximately 50% of survivors have a residual neurologic deficit and greater than 25% require chronic care. Cerebrovascular reserve capacity (CVRC) describes how far cerebral perfusion can increase from a baseline value after stimulation. High blood pressure is the most important independent risk factor for stroke and other vascular diseases. The incidence of stroke in the hypertensive is six times higher than in the patient with normal blood pressure. CVRC in the hypertensive was even lower than in control patients. MR perfusion weighted imaging (MR PWI) with the well-established acetazolamide (ACZ) stimulation test has been used for assessing brain function. The aim of this work is to assess the cerebrovascular reserve capacity by MR PWI with "ACZ" tolerance test in spontaneous hypertensive rat (SHR) and to identify its value in evaluating the CVRC. Experimental animal including 3 groups: Wistar-Kyoto rats (WKY) (12-week-old) as control group, SHR (12-week-old and 20-week-old) as experimental group. MR PWI was performed respectively before and after acetazolamide administrated orally in 3 groups on a clinical 1.5 Tesla GE Signa MR fx/i whole-body MR system. The ROI was chosen in the bilateral frontal lobe to measure the value of rCBV, rCBF and MTT. The results showed that before ACZ-test, there was statistic differences between the WKY and SHR(12-week-old), and between SHR(12-week-old) and SHR(20-week-old) in the values of rCBV and rCBF (P>0.05), and after ACZ-test, there were statistic differences between WKY and SHR (20-week-old), and between SHR(12-week-old) and SHR(20-week-old) in the rCBV value (P<0.05). It is concluded that the method of MRI PWI combined with the "ACZ stress test" can provide more qualitative and half-quantitative information on the cerebral perfusion to evaluate the CVRC in SHR.

[Effect of curcumine on the nuclear pathway of JNK during hippocampal ischemia/reperfusion injury in SHR].

PubMed

Ye, Ke-Ping; Chen, Chun-Ru; Zheng, Jin-Wei; Cao, Hong; Ji, Bin; Zhou, Rui; Meng, Zhi-Yan; Li, Jun; Lian, Qing-Quan

2010-11-01

To investigate the diversify of the nuclear pathway of c-Jun NH2-terminal kinases (JNK) during transient brain ischemia/reperfusion injury in hippocampal neuron apoptosis in spontaneously hypertensive rats (SHR) and to test whether the neuroprotection of curcumine on transient brain ischemia/reperfusion injury in SHR is related to the nuclear pathway of JNK. Male Wistar-Kyoto (WKY) rats and SHR were randomly divided into five groups (n = 6): WKY sham group (W-Sham), WKY ischemia/reperfusion group (W-I/ R), SHR sham group (S-Sham), SHR ischemia/reperfusion group (S-I/R) and SHR curcumine (a chinese traditional medicine)100 mg/kg treatment group (S-Cur), which were sacrificed at 2 h, 6 h, 24 h, 3 d and 7 d after reperfusion. Global brain ischemic model was established by 4-VO method. The TdT-mediated dUTP nick end labeling (TUNEL) method was used to detect the neuron apoptosis in hippocampal CA1 region. The immunohistochemical method was applied to investigate the expressions of c-jun and c-fos in hippocampal CA1 region. The expressions of apoptosis and c-jun and c-fos in CA1 region in S-Sham group, W-I/R group and S-I/R group were more than those in W-Sham group (P < 0.05), were significantly increased in S-I/R group than those in W-I/R group (P < 0.05), and were significantly decreased in S-Cur group than those in S-I/R group (P < 0.05). Neuronal apoptosis and the expressions of c-jun and c-fos are more in SHR hippocampal. Global brain ischemia/reperfusion injury induces more expressions of apoptosis in hippocampal neuron in SHR, and the more expressions of c-jun and c-fos may participate in that process. The neuroprotection of curcumine in SHR is related to c-jun and c-fos.

[MK-801 or DNQX reduces electroconvulsive shock-induced impairment of learning-memory and hyperphosphorylation of Tau in rats].

PubMed

Liu, Chao; Min, Su; Wei, Ke; Liu, Dong; Dong, Jun; Luo, Jie; Liu, Xiao-Bin

2012-08-25

This study explored the effect of the excitatory amino acid receptor antagonists on the impairment of learning-memory and the hyperphosphorylation of Tau protein induced by electroconvulsive shock (ECT) in depressed rats, in order to provide experimental evidence for the study on neuropsychological mechanisms improving learning and memory impairment and the clinical intervention treatment. The analysis of variance of factorial design set up two intervention factors which were the electroconvulsive shock (two level: no disposition; a course of ECT) and the excitatory amino acid receptor antagonists (three level: iv saline; iv NMDA receptor antagonist MK-801; iv AMPA receptor antagonist DNQX). Forty-eight adult Wistar-Kyoto (WKY) rats (an animal model for depressive behavior) were randomly divided into six experimental groups (n = 8 in each group): saline (iv 2 mL saline through the tail veins of WKY rats ); MK-801 (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats) ; DNQX (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats ); saline + ECT (iv 2 mL saline through the tail veins of WKY rats and giving a course of ECT); MK-801 + ECT (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats and giving a course of ECT); DNQX + ECT (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats and giving a course of ECT). The Morris water maze test started within 1 day after the finish of the course of ECT to evaluate learning and memory. The hippocampus was removed from rats within 1 day after the finish of Morris water maze test. The content of glutamate in the hippocampus of rats was detected by high performance liquid chromatography. The contents of Tau protein which included Tau5 (total Tau protein), p-PHF1(Ser396/404), p-AT8(Ser199/202) and p-12E8(Ser262) in the hippocampus of rats were detected by immunohistochemistry staining (SP) and Western blot. The results showed that ECT and the glutamate ionic receptor blockers (NMDA receptor antagonist MK-801 and

Trpv4 involvement in the sex differences in blood pressure regulation in spontaneously hypertensive rats.

PubMed

Onishi, Makiko; Yamanaka, Ko; Miyamoto, Yasunori; Waki, Hidefumi; Gouraud, Sabine

2018-04-01

Arterial pressure (AP) is lower in premenopausal women than in men of a similar age. Premenopausal women exhibit a lower sympathetic activity and a greater baroreceptor reflex; however, mechanisms controlling sex differences in blood pressure regulation are not well understood. We hypothesized that different neuronal functions in the cardiovascular centers of the brains of men and women may contribute to the sex difference in cardiovascular homeostasis. Our previous studies on male spontaneously hypertensive rats (SHRs) and their normotensive counterparts, Wistar Kyoto (WKY) rats, revealed that the gene-expression profile of the nucleus tractus solitarius (NTS), a region of the medulla oblongata that is pivotal for regulating the set point of AP, is strongly associated with AP. Thus, we hypothesized that gene-expression profiles in the rat NTS are related to sex differences in AP regulation. Because female SHRs clearly exhibit lower AP than their male counterparts of a similar age, we investigated whether SHR NTS exhibits sex differences in gene expression by using microarray and RT-qPCR experiments. The transcript for transient receptor potential cation channel subfamily V member 4 ( Trpv4) was found to be upregulated in SHR NTS in females compared with that in males. The channel was expressed in neurons and glial cells within NTS. The TRPV4 agonist 4-alpha-phorbol-12,13-didecanoate (4α-PDD) decreased blood pressure when injected into NTS of rats. These findings suggest that altered TRPV4 expression might be involved in the sex differences in blood pressure regulation.

Influence of outdoor advertisement colors on psychological evaluation of townscape in Kyoto

NASA Astrophysics Data System (ADS)

Onishi, Ayumi; Ishida, Taiichiro; Katsuya, Yoshiko

2002-06-01

Outdoor advertisements must be one of the major factors that affect our psychological impression for townscapes. They often conflict with propr color environments in cities particularly in historic cities like Kyoto. In this study we investigated how outdoor advertisements influenced our visual evaluation of townscapes in Kyoto. In recent years, a new regulation for outdoor advertisements came into operation in Kyoto and some of the advertisements have been replaced or removed gradually. We examined psychological evaluation for the townscapes before and after their changes. In the experiment, subjects evaluated 'visual harmony,' 'visual busyness,' 'visual comfort' and 'suitability to Kyoto' of townscapes projected on a screen. The results indicated that the evaluation of 'visual busyness' significantly decreased with the amount of the advertisements. The relations between the advertisements and the psychological evaluation of the townscape are discussed.

Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain.

PubMed

Moloney, Rachel D; Golubeva, Anna V; O'Connor, Richard M; Kalinichev, Mikhail; Dinan, Timothy G; Cryan, John F

2015-01-01

Glutamate, the main excitatory neurotransmitter in the central nervous system, exerts its effect through ionotropic and metabotropic receptors. Of these, group III mGlu receptors (mGlu 4, 6, 7, 8) are among the least studied due to a lack of pharmacological tools. mGlu7 receptors, the most highly conserved isoform, are abundantly distributed in the brain, especially in regions, such as the amygdala, known to be crucial for the emotional processing of painful stimuli. Visceral hypersensitivity is a poorly understood phenomenon manifesting as an increased sensitivity to visceral stimuli. Glutamate has long been associated with somatic pain processing leading us to postulate that crossover may exist between these two modalities. Moreover, stress has been shown to exacerbate visceral pain. ADX71743 is a novel, centrally penetrant, negative allosteric modulator of mGlu7 receptors. Thus, we used this tool to explore the possible involvement of this receptor in the mediation of visceral pain in a stress-sensitive model of visceral hypersensitivity, namely the Wistar Kyoto (WKY) rat. ADX71743 reduced visceral hypersensitivity in the WKY rat as exhibited by increased visceral sensitivity threshold with concomitant reductions in total number of pain behaviours. Moreover, AD71743 increased total distance and distance travelled in the inner zone of the open field. These findings show, for what is to our knowledge, the first time, that mGlu7 receptor signalling plays a role in visceral pain processing. Thus, negative modulation of the mGlu7 receptor may be a plausible target for the amelioration of stress-induced visceral pain where there is a large unmet medical need.

Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain

PubMed Central

Moloney, Rachel D.; Golubeva, Anna V.; O'Connor, Richard M.; Kalinichev, Mikhail; Dinan, Timothy G.; Cryan, John F.

2015-01-01

Glutamate, the main excitatory neurotransmitter in the central nervous system, exerts its effect through ionotropic and metabotropic receptors. Of these, group III mGlu receptors (mGlu 4, 6, 7, 8) are among the least studied due to a lack of pharmacological tools. mGlu7 receptors, the most highly conserved isoform, are abundantly distributed in the brain, especially in regions, such as the amygdala, known to be crucial for the emotional processing of painful stimuli. Visceral hypersensitivity is a poorly understood phenomenon manifesting as an increased sensitivity to visceral stimuli. Glutamate has long been associated with somatic pain processing leading us to postulate that crossover may exist between these two modalities. Moreover, stress has been shown to exacerbate visceral pain. ADX71743 is a novel, centrally penetrant, negative allosteric modulator of mGlu7 receptors. Thus, we used this tool to explore the possible involvement of this receptor in the mediation of visceral pain in a stress-sensitive model of visceral hypersensitivity, namely the Wistar Kyoto (WKY) rat. ADX71743 reduced visceral hypersensitivity in the WKY rat as exhibited by increased visceral sensitivity threshold with concomitant reductions in total number of pain behaviours. Moreover, AD71743 increased total distance and distance travelled in the inner zone of the open field. These findings show, for what is to our knowledge, the first time, that mGlu7 receptor signalling plays a role in visceral pain processing. Thus, negative modulation of the mGlu7 receptor may be a plausible target for the amelioration of stress-induced visceral pain where there is a large unmet medical need. PMID:26844237

Autoimmunity to the alpha 3 chain of type IV collagen in glomerulonephritis is triggered by ‘autoantigen complementarity’

PubMed Central

Reynolds, John; Preston, Gloria A.; Pressler, Barrak M.; Hewins, Peter; Brown, Michael; Roth, Aleeza; Alderman, Elizabeth; Bunch, Donna; Jennette, J. Charles; Cook, H. Terence; Falk, Ronald J.; Pusey, Charles D.

2015-01-01

‘Autoantigen complementarity’ is a theory proposing that the initiator of an autoimmune response is not necessarily the autoantigen or its molecular mimic, but may instead be a peptide that is ‘antisense/complementary’ to the autoantigen. We investigated whether such complementary proteins play a role in the immunopathogenesis of autoimmune glomerulonephritis. Experimental autoimmune glomerulonephritis, a model of anti-glomerular basement membrane (GBM) disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the α3 chain of type IV collagen. In this study, WKY rats were immunized with a complementary α3 peptide (c-α3-Gly) comprised of amino acids that ‘complement’ the well characterized epitope on α3(IV)NC1, pCol(24–38). Within 8 weeks post-immunization, these animals developed cresentic glomerulonephritis, similar to pCol(24–38)-immunized rats, while animals immunized with scrambled peptide were normal. Anti-idiotypic antibodies to epitopes from c-α3-Gly-immunized animals were shown to be specific for α3 protein, binding in a region containing sense pCol(24–38) sequence. Interestingly, anticomplementary α3 antibodies were identified in sera from patients with anti-GBM disease, suggesting a role for ‘autoantigen complementarity’ in immunopathogenesis of the human disease. This work supports the idea that autoimmune glomerulonephritis can be initiated through an immune response against a peptide that is anti-sense or complementary to the autoantigen. The implications of this discovery may be far reaching, and other autoimmune diseases could be due to responses to these once unsuspected ‘complementary’ antigens. PMID:25841937

CaMKII Regulates Synaptic NMDA Receptor Activity of Hypothalamic Presympathetic Neurons and Sympathetic Outflow in Hypertension.

PubMed

Li, De-Pei; Zhou, Jing-Jing; Zhang, Jixiang; Pan, Hui-Lin

2017-11-01

NMDAR activity in the hypothalamic paraventricular nucleus (PVN) is increased and critically involved in heightened sympathetic vasomotor tone in hypertension. Calcium/calmodulin-dependent protein kinase II (CaMKII) binds to and modulates NMDAR activity. In this study, we determined the role of CaMKII in regulating NMDAR activity of PVN presympathetic neurons in male spontaneously hypertensive rats (SHRs). NMDAR-mediated EPSCs and puff NMDA-elicited currents were recorded in spinally projecting PVN neurons in SHRs and male Wistar-Kyoto (WKY) rats. The basal amplitude of evoked NMDAR-EPSCs and puff NMDA currents in retrogradely labeled PVN neurons were significantly higher in SHRs than in WKY rats. The CaMKII inhibitor autocamtide-2-related inhibitory peptide (AIP) normalized the increased amplitude of NMDAR-EPSCs and puff NMDA currents in labeled PVN neurons in SHRs but had no effect in WKY rats. Treatment with AIP also normalized the higher frequency of NMDAR-mediated miniature EPSCs of PVN neurons in SHRs. CaMKII-mediated phosphorylation level of GluN2B serine 1303 (S1303) in the PVN, but not in the hippocampus and frontal cortex, was significantly higher in SHRs than in WKY rats. Lowering blood pressure with celiac ganglionectomy in SHRs did not alter the increased level of phosphorylated GluN2B S1303 in the PVN. In addition, microinjection of AIP into the PVN significantly reduced arterial blood pressure and lumbar sympathetic nerve discharges in SHRs. Our findings suggest that CaMKII activity is increased in the PVN and contributes to potentiated presynaptic and postsynaptic NMDAR activity to elevate sympathetic vasomotor tone in hypertension. SIGNIFICANCE STATEMENT Heightened sympathetic vasomotor tone is a major contributor to the development of hypertension. Although glutamate NMDA receptor (NMDAR)-mediated excitatory drive in the hypothalamus plays a critical role in increased sympathetic output in hypertension, the molecular mechanism involved in

Defective trophoblast invasion underlies fetal growth restriction and preeclampsia-like symptoms in the stroke-prone spontaneously hypertensive rat.

PubMed

Barrientos, G; Pussetto, M; Rose, M; Staff, A C; Blois, S M; Toblli, J E

2017-07-01

What is the impact of chronic hypertension on placental development, fetal growth and maternal outcome in the stroke-prone spontaneously hypertensive rat (SHRSP)? SHRSP showed an impaired remodeling of the spiral arteries and abnormal pattern of trophoblast invasion during placentation, which were associated with subsequent maternal glomerular injury and increased baseline hypertension as well as placental insufficiency and asymmetric fetal growth restriction (FGR). A hallmark in the pathogenesis of preeclampsia (PE) is abnormal placentation with defective remodeling of the spiral arteries preceding the onset of the maternal syndrome. Pregnancies affected by chronic hypertension display an increased risk for PE, often associated with poor maternal and fetal outcomes. However, the impact of chronic hypertension on the placentation process as well as the nature of the factors promoting the development of PE in pregnant hypertensive women remain elusive. Timed pregnancies [n = 5] were established by mating 10-12-week-old SHRSP and Wistar Kyoto (WKY, normotensive controls) females with congenic males. Maternal systolic blood pressures (SBPs) were recorded pre-mating, throughout pregnancy (GD1-19) and post-partum by the tail-cuff method. On selected dates, 24 h urine- and blood samples were collected, and animals were euthanized for isolation of implantation sites and kidneys for morphometrical analyses. The 24 h proteinuria and the albumin:creatinine ratio were used for evaluation of maternal renal function. Renal injury was assessed on periodic acid Schiff, Masson's trichrome and Sirius red stainings. Placental and fetal weights were recorded on gestation day (GD)18 and GD20, followed by determination of fetal cephalization indexes and developmental stage, according to the Witschi scale. Morphometric analyses of placental development were conducted on hematoxylin-eosin stained tissue sections collected on GD14 and GD18, and complemented with immunohistochemical

Branched-chain amino acid-rich diet improves skeletal muscle wasting caused by cigarette smoke in rats.

PubMed

Tomoda, Koichi; Kubo, Kaoru; Hino, Kazuo; Kondoh, Yasunori; Nishii, Yasue; Koyama, Noriko; Yamamoto, Yoshifumi; Yoshikawa, Masanori; Kimura, Hiroshi

2014-04-01

Cigarette smoke induces skeletal muscle wasting by a mechanism not yet fully elucidated. Branched-chain amino acids (BCAA) in the skeletal muscles are useful energy sources during exercise or systemic stresses. We investigated the relationship between skeletal muscle wasting caused by cigarette smoke and changes in BCAA levels in the plasma and skeletal muscles of rats. Furthermore, the effects of BCAA-rich diet on muscle wasting caused by cigarette smoke were also investigated. Wistar Kyoto (WKY) rats that were fed with a control or a BCAA-rich diet were exposed to cigarette smoke for four weeks. After the exposure, the skeletal muscle weight and BCAA levels in plasma and the skeletal muscles were measured. Cigarette smoke significantly decreased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles, while a BCAA-rich diet increased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles that had decreased by cigarette smoke exposure. In conclusion, skeletal muscle wasting caused by cigarette smoke was related to the decrease of BCAA levels in the skeletal muscles, while a BCAA-rich diet may improve cases of cigarette smoke-induced skeletal muscle wasting.

Acute blood pressure effects of YC-1-induced activation of soluble guanylyl cyclase in normotensive and hypertensive rats

PubMed Central

Rothermund, Lars; Friebe, Andreas; Paul, Martin; Koesling, Doris; Kreutz, Reinhold

2000-01-01

We used YC-1 as a pharmacological tool to investigate the short-term blood pressure effects of NO-independent activation of sGC in normotensive and hypertensive rats. Four groups of normotensive Wistar-Kyoto rats were treated by i.v. injection with vehicle (V), YC-1 (YC-1), sodium nitroprusside (SNP), or YC-1 and SNP (YC-1+SNP). Hypertension was induced in four additional groups of WKY rats by 3 weeks of oral treatment with L-NAME. These animals were investigated with the same protocol as the normotensive animals: L-NAME/V, L-NAME/YC-1, L-NAME/SNP, L-NAME/YC-1+SNP. YC-1 lowered mean arterial blood pressure (MAP) in normotensive and hypertensive animals similarly to SNP alone (P<0.05, respectively). The combination of YC-1 with SNP caused a strong decrease of MAP in both the hypertensive and normotensive animals (P<0.05, respectively). SNP with YC-1 also induced a pronounced cyclic GMP increase in the aorta. This study shows for the first time the blood pressure lowering potential of bimodal targeting of the NO-sGC-system. PMID:10807655

THE ROLE OF OXIDATIVE STRESS AND MITOCHONDRIA IN PARTICULATE MATTER (PM)-INDUCED CARDIOPULMONARY INJURY IN STROKE PRONE SPONTANEOUSLY HYPERTENSIVE (SHRSP) AND WISTAR KYOTO (WKY) RATS

EPA Science Inventory

Epidemiological studies have associated PM exposure with cardiovascular mortality and morbidity, and this effect seems to be enhanced in populations with pre-existing cardiovascular disease. One hypothesis for this exacerbation is that the higher underlying level of oxidative st...

Comparison of posture and balance in cancer survivors and age-matched controls.

PubMed

Schmitt, Abigail C; Repka, Chris P; Heise, Gary D; Challis, John H; Smith, Jeremy D

2017-12-01

The combination of peripheral neuropathy and other treatment-associated side effects is likely related to an increased incidence of falls in cancer survivors. The purpose of this study was to quantify differences in postural stability between healthy age-matched controls and cancer survivors. Quiet standing under four conditions (eyes open/closed, rigid/compliant surface) was assessed in 34 cancer survivors (2 males, 32 females; age: 54(13) yrs., height: 1.62(0.07) m; mass: 78.5(19.5) kg) and 34 age-matched controls (5 males, 29 females; age: 54(15) yrs.; height: 1.62(0.08) m; mass: 72.8(21.1) kg). Center of pressure data were collected for 30s and the trajectories were analyzed (100Hz). Three-factor (group*surface*vision) mixed model MANOVAs with repeated measures were used to determine the effect of vision and surface on postural steadiness between groups. Cancer survivors exhibited larger mediolateral root-mean square distance and velocity of the center of pressure, as well as increased 95% confidence ellipse area (P<0.01) when compared with their age-matched counterparts. For example, when removing visual input, cancer survivors had an average increase in 95% confidence ellipse area of 91.8mm 2 while standing on a rigid surface compared to a 68.6mm 2 increase for the control group. No frequency-based center of pressure measures differed between groups. Cancer survivors exhibit decreased postural steadiness when compared with age-matched controls. For cancer survivors undergoing rehabilitation focused on existing balance deficits, a small subset of the center of pressure measures presented here can be used to track progress throughout the intervention and potentially mitigate fall risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

Forced ethanol ingestion by Wistar rats from a juvenile age increased voluntary alcohol consumption in adulthood, with the involvement of orexin-A.

PubMed

Mendoza-Ruiz, Luis-Gabriel; Vázquez-León, Priscila; Martínez-Mota, Lucía; Juan, Eduardo Ramírez San; Miranda-Páez, Abraham

2018-08-01

Human adolescents who drink alcohol are more likely to become alcoholics in adulthood. Alcohol administration (intraperitoneally) or drinking (in a 2-bottle free choice paradigm) during the juvenile/adolescent age of rats promotes voluntary alcohol consumption in adulthood. On the other hand, there is growing evidence that the orexinergic system plays a role in several rewarded behaviors, including alcohol ingestion. Since it is unknown what effect is exerted in adulthood by forced oral ethanol intake and/or administration of orexin-A (OX-A) in juvenile rats, the present study aimed to evaluate this question. A group of male Wistar rats was forced to drink ethanol (10% v/v) as the only liquid in the diet from weaning (postnatal day 21) to postnatal day 67 (46 days), followed by a forced withdrawal period. An age-matched group was raised drinking tap water (control). OX-A or its vehicle was microinjected intracerebroventricularly (i.c.v.) (1 nmol/0.6 μL) to explore its effect as well. Locomotor activity and voluntary ethanol consumption were later assessed in all groups. The rats forced to consume ethanol early in life showed an elevated level of ambulation and alcohol ingestion in adulthood. A single injection of OX-A increased locomotor activity and acute ethanol intake in rats with or without prior exposure to alcohol at the juvenile stage. In conclusion, forced ethanol consumption in juvenile rats led to increased voluntary alcohol drinking behavior during adulthood, an effect likely facilitated by OX-A. Copyright © 2018 Elsevier Inc. All rights reserved.

Daily NO rhythms in peripheral clocks in aging male Wistar rats: protective effects of exogenous melatonin.

PubMed

Vinod, Ch; Jagota, Anita

2016-11-01

In mammals suprachiasmatic nucleus (SCN), acts as a light entrainable master clock and by generation of temporal oscillations regulates the peripheral organs acting as autonomous clocks resulting in overt behavioral and physiological rhythms. SCN also controls synthesis and release of melatonin (hormonal message for darkness) from pineal. Nitric Oxide (NO) acts as an important neurotransmitter in generating the phase shifts of circadian rhythms and participates in sleep-wake processes, maintenance of vascular tone as well as signalling and regulating inflammatory processes. Aging is associated with disruption of circadian timing system and decline in endogenous melatonin leading to several physiological disorders. Here we report the effect of aging on NO daily rhythms in various peripheral clocks such as kidney, intestine, liver, heart, lungs and testis. NO levels were measured at zeitgeber time (ZT) 0, 6, 12 and 18 in these tissues using Griess assay in male Wistar rats. Aging resulted in alteration of NO levels as well as phase of NO in both 12 and 24 months groups. Correlation analysis demonstrated loss of stoichiometric interaction between the various peripheral clocks with aging. Age induced alterations in NO daily rhythms were found to be most significant in liver and, interestingly least in lungs. Neurohormone melatonin, an endogenous synchroniser and an antiaging agent decreases with aging. We report further differential restoration with exogenous melatonin administration of age induced alterations in NO daily rhythms and mean levels in kidney, intestine and liver and the stoichiometric interactions between the various peripheral clocks.

Climate change. Managing forests after Kyoto.

PubMed

Schulze, D E; Wirth, C; Heimann, M

2000-09-22

The Kyoto protocol aims to reduce carbon emissions into the atmosphere. Part of the strategy is the active management of terrestrial carbon sinks, principally through afforestation and reforestation. In their Perspective, Schulze et al. argue that the preservation of old-growth forests may have a larger positive effect on the carbon cycle than promotion of regrowth.

Effects of age, maturity and body dimensions on match running performance in highly trained under-15 soccer players.

PubMed

Buchheit, Martin; Mendez-Villanueva, Alberto

2014-01-01

The aim of the present study was to compare, in 36 highly trained under-15 soccer players, the respective effects of age, maturity and body dimensions on match running performance. Maximal sprinting (MSS) and aerobic speeds were estimated. Match running performance was analysed with GPS (GPSport, 1 Hz) during 19 international friendly games (n = 115 player-files). Total distance and distance covered >16 km h(-1) (D > 16 km h(-1)) were collected. Players advanced in age and/or maturation, or having larger body dimensions presented greater locomotor (Cohen's d for MSS: 0.5-1.0, likely to almost certain) and match running performances (D > 16 km h(-1): 0.2-0.5, possibly to likely) than their younger, less mature and/or smaller teammates. These age-, maturation- and body size-related differences were of larger magnitude for field test measures versus match running performance. Compared with age and body size (unclear to likely), maturation (likely to almost certainly for all match variables) had the greatest impact on match running performance. The magnitude of the relationships between age, maturation and body dimensions and match running performance were position-dependent. Within a single age-group in the present player sample, maturation had a substantial impact on match running performance, especially in attacking players. Coaches may need to consider players' maturity status when assessing their on-field playing performance.

Effects of gonadectomy and testosterone treatment on aquaporin expression in the kidney of normotensive and hypertensive rats.

PubMed

Loh, Su Yi; Giribabu, Nelli; Salleh, Naguib

2017-07-01

We tested the hypothesis that testosterone-induced increase in blood pressure was due to changes in aquaporin (AQP) expression in kidneys. In this study, expression level of kidney AQPs was investigated under testosterone influence. Adult normotensive Wistar Kyoto (WKY) and hypertensive SHR male and female rats underwent gonadectomy. For female rats, testosterone was given for six weeks duration, two weeks following ovariectomy via subcutaneous silastic implant. Mean arterial pressure (MAP) was measured in all the rats after eight weeks via carotid artery cannulation and the rats were then sacrificed and kidneys were harvested for analyses of AQP-1, 2, 3, 4, 6, and 7 mRNA and protein expressions by quantitative real-time PCR and Western blotting, respectively. Distribution of AQP subunits' protein in kidneys was observed by immunofluorescence. In male WKY rats, MAP, AQP-1, 2, 4, and 7 protein; and mRNA expression decreased however AQP-3 protein and mRNA expression increased following orchidectomy. The vice versa effects were observed in testosterone-treated ovariectomized female WKY rats. However, no changes in AQP-6 expression were observed. Meanwhile, in adult male SHR rats, MAP and expression level of all AQP subunits decreased following orchidectomy. The opposite effects were seen in ovariectomized female SHR rats following testosterone treatment. Immunofluorescence study showed AQP-1 and AQP-7 were distributed in the proximal convoluted tubules (PCT) while AQP-2, AQP-4, and AQP-6 were distributed in the collecting ducts (CDs). AQP-3 was distributed in the PCT and CD. In conclusion, changes in AQP subunit expression in kidneys could explain changes in blood pressure under testosterone influence. Impact statement This study provides fundamental understanding on the mechanisms underlying testosterone-induced increase in blood pressure which involve regulation of aquaporin channel subunits in the kidneys. A better understanding of this issue can help to explain

Autonomic control of ultradian and circadian rhythms of blood pressure, heart rate, and baroreflex sensitivity in spontaneously hypertensive rats.

PubMed

Oosting, J; Struijker-Boudier, H A; Janssen, B J

1997-04-01

To examine the influence of the autonomic nervous system on ultradian and circadian rhythms of blood pressure, heart rate and baroreflex sensitivity of heart rate (BRS) in spontaneously hypertensive rats (SHR). Spontaneous fluctuations in blood pressure, heart rate and BRS in SHR were recorded continuously for 24 h using a computerized system and compared with those in Wistar-Kyoto (WKY) rats. Furthermore, 24 h recordings were performed in SHR during cardiac autonomic blockade by metoprolol and methyl-atropine, vascular autonomic blockade by prazosin, ganglionic blockade by hexamethonium and vagal stimulation by a low dose of scopolamine. The magnitudes of the ultradian fluctuations in blood pressure, heart rate and BRS were assessed by wide-band spectral analysis techniques. The BRS was lower in SHR than it was in WKY rats throughout the 24 h cycle. In both strains high values were found during the light, resting period, whereas low values were found during the first hours of the dark, active period. The circadian rhythmicity of the blood pressure in SHR was abolished completely during the infusions of prazosin and hexamethonium. In contrast, the circadian rhythmicities of the blood pressure and heart rate were not altered by infusions of metoprolol, methyl-atropine and the low dose of scopolamine. Power spectra of the blood pressure and heart rate lacked predominant peaks at ultradian frequencies and showed 1/f characteristics. In the absence of autonomic tone, the ultradian fluctuations in heart rate, but not in blood pressure, were decreased. The ultradian BRS spectra had no 1/f shape, but showed a major peak at approximately equal to 20 min for 71% of the WKY rats and 42% of the SHR. The influence of the autonomic nervous system on the blood pressure and heart rats in SHR is frequency-dependent. The circadian, but not ultradian, blood pressure rhythmicity is controlled by vascular autonomic activity. Conversely, the circadian, but not ultradian, heart rate

Behavioral changes following PCB 153 exposure in the Spontaneously Hypertensive rat – an animal model of Attention-Deficit/Hyperactivity disorder

PubMed Central

2014-01-01

Background Attention-Deficit/Hyperactivity Disorder (ADHD) is a behavioral disorder affecting 3-5% of children. Although ADHD is highly heritable, environmental factors like exposure during early development to various toxic substances like polychlorinated biphenyls (PCBs) may contribute to the prevalence. PCBs are a group of chemical industrial compounds with adverse effects on neurobiological and cognitive functioning, and may produce behavioral impairments that share significant similarities with ADHD. The present study examined the relation between exposure to PCB 153 and changes in ADHD-like behavior in an animal model of ADHD, the spontaneously hypertensive rats (SHR/NCrl), and in Wistar Kyoto (WKY/NHsd) controls. Methods SHR/NCrl and WKY/NHsd, males and females, were orally given PCB 153 dissolved in corn oil at around postnatal day (PND) 8, 14, and 20 at a dosage of 1, 3 or 6 mg/kg bodyweight at each exposure. The control groups were orally administered corn oil only. The animals were behaviorally tested for exposure effects from PND 37 to 64 using an operant procedure. Results Exposure to PCB 153 was associated with pronounced and long-lasting behavioral changes in SHR/NCrl. Exposure effects in the SHR/NCrl depended on dose, where 1 mg/kg tended to reduce ADHD-like behaviors and produce opposite behavioral effects compared to 3 mg/kg and 6 mg/kg, especially in the females. In the WKY/NHsd controls and for the three doses tested, PCB 153 exposure produced a few specific behavioral changes only in males. The data suggest that PCB 153 exposure interacts with strain and sex, and also indicate a non-linear dose–response relation for the behaviors observed. Conclusions Exposure to PCB 153 seems to interact with several variables including strain, sex, dose, and time of testing. To the extent that the present findings can be generalized to humans, exposure effects of PCB 153 on ADHD behavior depends on amount of exposure, where high doses may aggravate ADHD

Nickel-regulated heart rate variability: The roles of oxidative stress and inflammation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chuang, Hsiao-Chi, E-mail: r92841005@ntu.edu.tw; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; Hsueh, Tzu-Wei, E-mail: r95841015@ntu.edu.tw

Heart rate variability (HRV) has been reported to be a putative marker of cardiac autonomic imbalance caused by exposure to ambient particulate matter (PM). Our objective in this study was to determine the effects on HRV from exposure to nickel, an important chemical component of ambient PM that results in oxidative stress and inflammation. HRV data were collected for 72 h before lung exposure (baseline) and 72 h after intratracheal exposure (response) to nickel sulphate (NiSO{sub 4}; 526 μg) in Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats. The antioxidant N-acetyl-L-cysteine (NAC) and the anti-inflammatory celecoxib were intraperitoneally injected tomore » examine post-exposure oxidative and inflammatory responses. Self-controlled experiments examined the effects of NiSO{sub 4} exposure on average normal-to-normal intervals (ANN), natural logarithm-transformed standard deviation of the normal-to-normal intervals (LnSDNN) and root mean square of successive differences of adjacent normal-to-normal intervals (LnRMSSD); the resulting data were sequentially analysed using the generalised estimating equation model. HRV effects on NiSO{sub 4}-exposed SH rats were greater than those on NiSO{sub 4}-exposed WKY rats. After adjusted the HRV responses in the WKY rats as control, ANN and LnRMSSD were found to be quadratically increased over 72 h after exposure to NiSO{sub 4}. Both NAC and celecoxib mitigated the NiSO{sub 4}-induced alterations in HRV during the exposure period. The results suggest that concurrent Ni-induced oxidative stress and inflammatory responses play important roles in regulating HRV. These findings help bridge the gap between epidemiological and clinical studies on the plausible mechanisms of the cardiovascular consequences induced by chemical components in ambient PM. -- Highlights: ► To determine the effects on HRV from exposure to nickel. ► ANN and LnRMSSD were found to be quadratically increased after exposure to Ni. ► NAC and

Analysis of the anxiolytic-like effect of TRH and the response of amygdalar TRHergic neurons in anxiety.

PubMed

Gutiérrez-Mariscal, Mariana; de Gortari, Patricia; López-Rubalcava, Carolina; Martínez, Adrián; Joseph-Bravo, Patricia

2008-02-01

Thyrotropin-releasing hormone (TRH) was first described for its neuroendocrine role in controlling the hypothalamus-pituitary-thyroid axis (HPT). Anatomical and pharmacological data evidence its participation as a neuromodulator in the central nervous system. Administration of TRH induces various behavioural effects including arousal, locomotion, analepsy, and in certain paradigms, it reduces fear behaviours. In this work we studied the possible involvement of TRHergic neurons in anxiety tests. We first tested whether an ICV injection of TRH had behavioural effects on anxiety in the defensive burying test (DBT). Corticosterone serum levels were quantified to evaluate the stress response and, the activity of the HPT axis to distinguish the endocrine response of TRH injection. Compared to a saline injection, TRH reduced cumulative burying, and decreased serum corticosterone levels, supporting anxiolytic-like effects of TRH administration. The response of TRH neurons was evaluated in brain regions involved in the stress circuitry of animals submitted to the DBT and to the elevated plus maze (EPM), tests that allow to correlate biochemical parameters with anxiety-like behaviour. In the DBT, the response of Wistar rats was compared with that of the stress-hypersensitive Wistar Kyoto (WKY) strain. Behavioural parameters were analysed in recorded videos. Animals were sacrificed 30 or 60min after test completion. In various limbic areas, the relative mRNA levels of TRH, its receptors TRH-R1 and -R2, and its inactivating ectoenzyme pyroglutamyl peptidase II (PPII), were determined by RT-PCR, TRH tissue content by radioimmunoassay (RIA). The extent of the stress response was evaluated by measuring the expression profile of CRH, CRH-R1 and GR mRNA in the paraventricular nucleus (PVN) of the hypothalamus and in amygdala, corticosterone levels in serum. As these tests demand increased physical activity, the response of the HPT axis was also evaluated. Both tasks increased the

Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat.

PubMed

Coan, Philip M; Hummel, Oliver; Garcia Diaz, Ana; Barrier, Marjorie; Alfazema, Neza; Norsworthy, Penny J; Pravenec, Michal; Petretto, Enrico; Hübner, Norbert; Aitman, Timothy J

2017-03-01

We previously mapped hypertension-related insulin resistance quantitative trait loci (QTLs) to rat chromosomes 4, 12 and 16 using adipocytes from F2 crosses between spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and subsequently identified Cd36 as the gene underlying the chromosome 4 locus. The identity of the chromosome 12 and 16 genes remains unknown. To identify whole-body phenotypes associated with the chromosome 12 and 16 linkage regions, we generated and characterised new congenic strains, with WKY donor segments introgressed onto an SHR genetic background, for the chromosome 12 and 16 linkage regions. We found a >50% increase in insulin sensitivity in both the chromosome 12 and 16 strains. Blood pressure and left ventricular mass were reduced in the two congenic strains consistent with the congenic segments harbouring SHR genes for insulin resistance, hypertension and cardiac hypertrophy. Integrated genomic analysis, using physiological and whole-genome sequence data across 42 rat strains, identified variants within the congenic regions in Upk3bl , RGD1565131 and AABR06087018.1 that were associated with blood pressure, cardiac mass and insulin sensitivity. Quantitative trait transcript analysis across 29 recombinant inbred strains showed correlation between expression of Hspb1 , Zkscan5 and Pdgfrl with adipocyte volume, systolic blood pressure and cardiac mass, respectively. Comparative genome analysis showed a marked enrichment of orthologues for human GWAS-associated genes for insulin resistance within the syntenic regions of both the chromosome 12 and 16 congenic intervals. Our study defines whole-body phenotypes associated with the SHR chromosome 12 and 16 insulin-resistance QTLs, identifies candidate genes for these SHR QTLs and finds human orthologues of rat genes in these regions that associate with related human traits. Further study of these genes in the congenic strains will lead to robust identification of the underlying genes and

Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat

PubMed Central

Hummel, Oliver; Garcia Diaz, Ana; Barrier, Marjorie; Alfazema, Neza; Norsworthy, Penny J.; Pravenec, Michal; Petretto, Enrico; Hübner, Norbert

2017-01-01

ABSTRACT We previously mapped hypertension-related insulin resistance quantitative trait loci (QTLs) to rat chromosomes 4, 12 and 16 using adipocytes from F2 crosses between spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and subsequently identified Cd36 as the gene underlying the chromosome 4 locus. The identity of the chromosome 12 and 16 genes remains unknown. To identify whole-body phenotypes associated with the chromosome 12 and 16 linkage regions, we generated and characterised new congenic strains, with WKY donor segments introgressed onto an SHR genetic background, for the chromosome 12 and 16 linkage regions. We found a >50% increase in insulin sensitivity in both the chromosome 12 and 16 strains. Blood pressure and left ventricular mass were reduced in the two congenic strains consistent with the congenic segments harbouring SHR genes for insulin resistance, hypertension and cardiac hypertrophy. Integrated genomic analysis, using physiological and whole-genome sequence data across 42 rat strains, identified variants within the congenic regions in Upk3bl, RGD1565131 and AABR06087018.1 that were associated with blood pressure, cardiac mass and insulin sensitivity. Quantitative trait transcript analysis across 29 recombinant inbred strains showed correlation between expression of Hspb1, Zkscan5 and Pdgfrl with adipocyte volume, systolic blood pressure and cardiac mass, respectively. Comparative genome analysis showed a marked enrichment of orthologues for human GWAS-associated genes for insulin resistance within the syntenic regions of both the chromosome 12 and 16 congenic intervals. Our study defines whole-body phenotypes associated with the SHR chromosome 12 and 16 insulin-resistance QTLs, identifies candidate genes for these SHR QTLs and finds human orthologues of rat genes in these regions that associate with related human traits. Further study of these genes in the congenic strains will lead to robust identification of the underlying

Remote Sensing and the Kyoto Protocol: A Workshop Summary

NASA Technical Reports Server (NTRS)

Rosenqvist, Ake; Imhoff, Marc; Milne, Anthony; Dobson, Craig

2000-01-01

The Kyoto Protocol to the United Nations Framework Convention on Climate Change contains quantified, legally binding commitments to limit or reduce greenhouse gas emissions to 1990 levels and allows carbon emissions to be balanced by carbon sinks represented by vegetation. The issue of using vegetation cover as an emission offset raises a debate about the adequacy of current remote sensing systems and data archives to both assess carbon stocks/sinks at 1990 levels, and monitor the current and future global status of those stocks. These concerns and the potential ratification of the Protocol among participating countries is stimulating policy debates and underscoring a need for the exchange of information between the international legal community and the remote sensing community. On October 20-22 1999, two working groups of the International Society for Photogrammetry and Remote Sensing (ISPRS) joined with the University of Michigan (Michigan, USA) to convene discussions on how remote sensing technology could contribute to the information requirements raised by implementation of, and compliance with, the Kyoto Protocol. The meeting originated as a joint effort between the Global Monitoring Working Group and the Radar Applications Working Group in Commission VII of the ISPRS, co-sponsored by the University of Michigan. Tile meeting was attended by representatives from national government agencies and international organizations and academic institutions. Some of the key themes addressed were: (1) legal aspects of transnational remote sensing in the context of the Kyoto Protocol; (2) a review of the current and future and remote sensing technologies that could be applied to the Kyoto Protocol; (3) identification of areas where additional research is needed in order to advance and align remote sensing technology with the requirements and expectations of the Protocol; and 94) the bureaucratic and research management approaches needed to align the remote sensing

In vivo inhibition of CC and CX3C chemokine-induced leukocyte infiltration and attenuation of glomerulonephritis in Wistar-Kyoto (WKY) rats by vMIP-II.

PubMed

Chen, S; Bacon, K B; Li, L; Garcia, G E; Xia, Y; Lo, D; Thompson, D A; Siani, M A; Yamamoto, T; Harrison, J K; Feng, L

1998-07-06

Chemokines play a central role in immune and inflammatory responses. It has been observed recently that certain viruses have evolved molecular piracy and mimicry mechanisms by encoding and synthesizing proteins that interfere with the normal host defense response. One such viral protein, vMIP-II, encoded by human herpesvirus 8, has been identified with in vitro antagonistic activities against CC and CXC chemokine receptors. We report here that vMIP-II has additional antagonistic activity against CX3CR1, the receptor for fractalkine. To investigate the potential therapeutic effect of this broad-spectrum chemokine antagonist, we studied the antiinflammatory activity of vMIP-II in a rat model of experimental glomerulonephritis induced by an antiglomerular basement membrane antibody. vMIP-II potently inhibited monocyte chemoattractant protein 1-, macrophage inflammatory protein 1beta-, RANTES (regulated on activation, normal T cell expressed and secreted)-, and fractalkine-induced chemotaxis of activated leukocytes isolated from nephritic glomeruli, significantly reduced leukocyte infiltration to the glomeruli, and markedly attenuated proteinuria. These results suggest that molecules encoded by some viruses may serve as useful templates for the development of antiinflammatory compounds.

Promoting health during the American occupation of Japan the public health section, Kyoto Military Government Team, 1945-1949.

PubMed

Nishimura, Sey

2008-03-01

During the American occupation of Japan (1945-1952), young public health officers from the US Army Medical Corps were posted in local US Army military government teams. These young doctors (aged 25 to 27 years), who had not absorbed the strong anti-Japanese tradition of the US military during World War II, seem to have alleviated the initial resentment felt by the Japanese toward the new governors of their homeland. The case of the Kyoto Military Government Team illustrates the Kyoto citizenry's positive view of some American-directed public health measures. The team's services helped to counter widely held negative views on colonialism, occupation, and public health; lessened resentment toward the unilateral command structure of the occupation forces; and contributed to improved relations between the United States and Japan at the local level.

Dynamic analysis of renal nerve activity responses to baroreceptor denervation in hypertensive rats.

PubMed

DiBona, G F; Jones, S Y

2001-04-01

Sinoaortic and cardiac baroreflexes exert important control over renal sympathetic nerve activity. Alterations in these reflex mechanisms contribute to renal sympathoexcitation in hypertension. Nonlinear dynamic analysis was used to examine the chaotic behavior of renal sympathetic nerve activity in normotensive Sprague-Dawley and Wistar-Kyoto rats and spontaneously hypertensive rats before and after complete baroreceptor denervation (sinoaortic and cardiac baroreceptor denervation). The peak interval sequence of synchronized renal sympathetic nerve discharge was extracted and used for analysis. In all rat strains, this yielded systems whose correlation dimensions converged to similar low values over the embedding dimension range of 10 to 15 and whose greatest Lyapunov exponents were positive. In Sprague-Dawley and Wistar-Kyoto rats, compete baroreceptor denervation was associated with decreases in the correlation dimensions (Sprague-DAWLEY: 2.42+/-0.04 to 2.16+/-0.04; Wistar-KYOTO: 2.44+/-0.04 to 2.34+/-0.04) and in the greatest Lyapunov exponents (Sprague-DAWLEY: 0.199+/-0.004 to 0.130+/-0.015; Wistar-KYOTO: 0.196+/-0.002 to 0.136+/-0.010). Spontaneously hypertensive rats had a similar correlation dimension, which was unaffected by complete baroreceptor denervation (2.42+/-0.02 versus 2.42+/-0.03), and a lower value for the greatest Lyapunov exponent, which decreased to a lesser extent after complete baroreceptor denervation (0.183+/-0.006 versus 0.158+/-0.006). These results indicate that removal of sinoaortic and cardiac baroreceptor regulation of renal sympathetic nerve activity is associated with a greater decrease in the chaotic behavior of renal sympathetic nerve activity in normotensive compared with hypertensive rats. This suggests that the central neural mechanisms that regulate renal sympathetic nerve activity in response to alterations in cardiovascular reflex inputs are different in spontaneously hypertensive rats from those in Sprague-Dawley and

Variation with age in the numbers of ovulated ova and follicles of Wistar-Imamichi adult rats superovulated with eCG-hCG.

PubMed

Kagabu, Satosi; Umezu, Motoaki

2006-01-01

There are large variations with age in the number of ovulated ova found in superovulated female Wistar-Imamichi rats. In this study we investigated the numbers of ovulated ova and follicles with the aim of developing a superovulation technique that minimises variations. We also examined the number of non-atretic follicles in untreated rats aged 7-14 weeks, for each week of age. The numbers of 250-549 microm non-atretic follicles in untreated rats and the numbers of ovulated ova in superovulated rats both reached a peak at 12 weeks of age. The coefficients of variation for both follicle numbers and ova numbers changed with each week of age, reaching a maximum at 9 weeks of age and a minimum at 12 weeks of age. In order to achieve stable numbers of ova from superovulated rats, satisfactory results will be achieved using 12-week-old rats, minimising individual variations, with high numbers of ova.

Education and Empty Relationality: Thoughts on Education and the Kyoto School of Philosophy

ERIC Educational Resources Information Center

Sevilla, Anton Luis

2016-01-01

This article builds on the growing literature on the Kyoto School of Philosophy and its influences on the field of Education. First, I argue that the influence of the Kyoto School of Philosophy is historically significant in Japan, and that the connection between this philosophical school and the philosophy of education is by no means superficial.…

Interaction of older donor age and survival after weight-matched pediatric heart transplantation.

PubMed

Westbrook, Thomas C; Morales, David L S; Khan, Muhammad S; Bryant, Roosevelt; Castleberry, Chesney; Chin, Clifford; Zafar, Farhan

2017-05-01

Donors are matched for weight in pediatric heart transplantation (PHT), yet age differences are not considered in this decision. In this study we attempt to identify the effect of age differences in weight-matched patients and the effect these differences have on post-transplant survival. The United Network of Organ Sharing (UNOS) database was queried for the period from October 1987 to March 2014 for all pediatric heart transplant patients. Transplants with donor-to-recipient (D-R) weight ratios of 0.8 to 1.5 were identified (weight-matched). D-R age differences were categorized as: donors 5 years younger than recipients (DR+5). A total of 4,408 patients were identified as weight-matched transplants. Of these transplants, 681 were D>R+5, 3,596 were D=R±5 and 131 were DR+5 transplants were found to be associated with decreased post-transplant survival compared with D=R±5 (p = 0.002). Rates of acute rejection were similar among all groups but post-transplant coronary allograft vasculopathy (CAV) was more prevalent in D>R+5 than D=R±5 patients (28% and 18%, respectively; p < 0.001). Increasing age difference by each year was associated with decreasing median post-transplant survival time (p < 0.001; hazard ratio 1.018, range 1.011 to 1.025). The overall negative association with mortality was due to the adolescent cohort (11 to 17 years), specifically D>R+5 transplants, utilizing organs from donors >25 of age. In PHT, increasing D-R age difference decreases survival; however, this effect is driven by recipients 11 to 17 years old and donors >25 years old. Allocation of younger donor organs to adolescent recipients should be a priority. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Promoting Health During the American Occupation of Japan The Public Health Section, Kyoto Military Government Team, 1945-1949

PubMed Central

Nishimura, Sey

2008-01-01

During the American occupation of Japan (1945–1952), young public health officers from the US Army Medical Corps were posted in local US Army military government teams. These young doctors (aged 25 to 27 years), who had not absorbed the strong anti-Japanese tradition of the US military during World War II, seem to have alleviated the initial resentment felt by the Japanese toward the new governors of their homeland. The case of the Kyoto Military Government Team illustrates the Kyoto citizenry’s positive view of some American-directed public health measures. The team’s services helped to counter widely held negative views on colonialism, occupation, and public health; lessened resentment toward the unilateral command structure of the occupation forces; and contributed to improved relations between the United States and Japan at the local level. PMID:18235076

Mucosal tolerance induced by an immunodominant peptide from rat alpha3(IV)NC1 in established experimental autoimmune glomerulonephritis.

PubMed

Reynolds, John; Abbott, Danielle S; Karegli, Julieta; Evans, David J; Pusey, Charles D

2009-06-01

Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture's disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the noncollagenous domain of the alpha 3 chain of type IV collagen, alpha3(IV)NC1. Recent studies have identified an immunodominant peptide, pCol (24-38), from the N-terminus of rat alpha3(IV)NC1; this peptide contains the major B- and T-cell epitopes in EAG and can induce crescentic nephritis. In this study, we investigated the mechanisms of mucosal tolerance in EAG by examining the effects of the nasal administration of this peptide after the onset of disease. A dose-dependent effect was observed: a dose of 300 microg had no effect, a dose of 1000 microg resulted in a moderate reduction in EAG severity, and a dose of 3000 microg produced a marked reduction in EAG severity accompanied by diminished antigen-specific, T-cell proliferative responses. These results demonstrate that mucosal tolerance in EAG can be induced by nasal administration of an immunodominant peptide from the N-terminus of alpha3(IV)NC1 and should be of value in designing new therapeutic strategies for patients with Goodpasture's disease and other autoimmune disorders.

Vasodilator activity of the essential oil from aerial parts of Pectis brevipedunculata and its main constituent citral in rat aorta.

PubMed

Pereira, Sharlene Lopes; Marques, André Mesquita; Sudo, Roberto Takashi; Kaplan, Maria Auxiliadora Coelho; Zapata-Sudo, Gisele

2013-03-07

The essential oil of Pectis brevipedunculata (EOPB), a Brazilian ornamental aromatic grass, is characterized by its high content of citral (81.9%: neral 32.7% and geranial 49.2%), limonene (4.7%) and α-pinene (3.4%). Vasodilation induced by EOPB and isolated citral was investigated in pre-contracted vascular smooth muscle, using thoracic aorta from Wistar Kyoto (WKY) rats which was prepared for isometric tension recording. EOPB promoted intense relaxation of endothelium-intact and denuded aortic rings with the concentration to induce 50% of the maximal relaxation (IC50) of 0.044% ± 0.006% and 0.093% ± 0.015% (p < 0.05), respectively. The IC50 values for citral in endothelium-intact and denuded rings were 0.024% ± 0.004% and 0.021% ± 0.004%, respectively (p > 0.05). In endothelium-intact aorta, EOPB-induced vasorelaxation was significantly reduced by L-NAME, a nitric oxide synthase inhibitor. The vasodilator activity of citral was increased in the KCl-contracted aorta and citral attenuated the contracture elicited by Ca2+ in depolarized aorta. EOPB and citral elicited vasorelaxation on thoracic aorta by affecting the NO/cyclic GMP pathway and the calcium influx through voltage-dependent L-type Ca2+ channels, respectively.

Effects of Red Palm Oil on Myocardial Antioxidant Enzymes, Nitric Oxide Synthase and Heart Function in Spontaneously Hypertensive Rats.

PubMed

Katengua-Thamahane, Emma; Szeiffova Bacova, Barbara; Bernatova, Iveta; Sykora, Matus; Knezl, Vladimir; Van Rooyen, Jacques; Tribulova, Narcis

2017-11-21

The purpose of this study was to investigate the effect of antioxidants rich red palm oil (RPO) supplementation on cardiac oxidative stress known as crucial factor deteriorating heart function in hypertension. 3-month-old, male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were fed standard rat chow without or with RPO (0.2 mL/day/5 weeks). General characteristic of rats were registered. Left ventricular tissue (LV) was used to determine expression of superoxide dismutases (SOD1, SOD2) and glutathione peroxidases (Gpx) as well as activity of nitric oxide synthase (NOS). Functional parameters of the heart were examined during basal conditions and at the early-phase of post-ischemic reperfusion using Langendorff-perfused system. RPO intake significantly reduced elevated blood pressure and total NOS activity as well as increased lowered expression of mitochondrial SOD2 in SHR hearts during basal condition. Moreover, RPO supplementation resulted in suppression of elevated heart rate, increase of reduced coronary flow and enhancement of systolic and diastolic heart function at the early-phase of post-ischemic reperfusion. It is concluded that SHR benefit from RPO intake due to decrease of blood pressure, amelioration of oxidative stress and protection of heart function that was deteriorated by post-ischemic reperfusion.

Enhancing hepatic fibrosis in spontaneously hypertensive rats fed a choline-deficient diet: a follow-up report on long-term effects of oxidative stress in non-alcoholic fatty liver disease.

PubMed

Yamamoto, Hiroya; Kanno, Keishi; Ikuta, Takuya; Arihiro, Koji; Sugiyama, Akiko; Kishikawa, Nobusuke; Tazuma, Susumu

2016-05-01

We previously reported a model of non-alcoholic fatty liver disease (NAFLD) using spontaneously hypertensive rats (SHRs), fed a choline-deficient (CD) diet for 5 weeks, that hepatic steatosis but not fibrosis is developed through oxidative stress. To determine the relationship between hypertension and hepatic fibrosis in NAFLD, we examined whether long-term CD diet leads to hepatic fibrosis through oxidative stress. Eight-week-old male SHR and normotensive Wistar Kyoto rats (WKYs) were fed a CD diet for 5 or 20 weeks, then liver histology and hepatic expression of genes related to lipid metabolism, fibrosis, and oxidative stress were assessed. Oxidative stress was assessed by hepatic thiobarbituric acid reactive substance (TBARS) levels. After 5 weeks on CD diet, prominent hepatic steatosis and decrease in expression of genes for lipid metabolism were observed in SHRs as compared with WKYs. SHRs on a CD diet demonstrated a downregulated expression of genes for antioxidants, along with significant increases in hepatic TBARS. After 20 weeks on CD diet, SHRs demonstrated severe liver fibrosis and upregulated expressions of genes for fibrosis when compared with WKY. Hypertension precipitated hepatic steatosis, and further, acts as an enhancer in NAFLD progression to liver fibrosis through oxidative stress. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Lecithin derived from ω-3 PUFA fortified eggs decreases blood pressure in spontaneously hypertensive rats.

PubMed

Nowacki, Dorian; Martynowicz, Helena; Skoczyńska, Anna; Wojakowska, Anna; Turczyn, Barbara; Bobak, Łukasz; Trziszka, Tadeusz; Szuba, Andrzej

2017-09-28

Hypertension is the most common risk factor for stroke, coronary heart disease and heart failure, which are the leading causes of death worldwide. Dietary patterns and supplements intakes are becoming important factors in the hypertension. The aim of this study was to estimate the effects of new generation egg yolk phospholipids rich in lecithin (SL) esterified with omega-3 and omega-6 fatty acids on blood pressure in hypertensive rats (SHR). Here we have reported that lecithin (SL) derived from egg yolk lowers blood pressure in pathology of hypertension. The SHR rats treated with SL had significantly lower blood pressure than control group (157/104 vs. 178/121 mmHg; P < 0.05) and down-regulated mesenteric artery over-response to norepinephrine and potassium chloride, giving similar arterial response as for normotensive Wistar Kyoto rats (WKY). Hypertensive rats treated by SL demonstrated significantly lower serum level of inflammatory factors. This work also indicates that SL treatment lowers heart rate and reduces the serum level of oxidative stress marker - nitrotyrosine - by 30-34% in both hypertensive and normotensive animals. Phospholipids with lecithin derived from PUFA fortified eggs may be a valuable dietary supplement in prophylaxis of hypertension and in patients with hypertension, however, this requires further studies on humans.

Increased glutamate-stimulated norepinephrine release from prefrontal cortex slices of spontaneously hypertensive rats.

PubMed

Russell, V A; Wiggins, T M

2000-12-01

Spontaneously hypertensive rats (SHR) have behavioral characteristics (hyperactivity, impulsiveness, poorly sustained attention) similar to the behavioral disturbances of children with attention-deficit hyperactivity disorder (ADHD). We have previously shown that dopaminergic and noradrenergic systems are disturbed in the prefrontal cortex of SHR compared to their normotensive Wistar-Kyoto (WKY) control rats. It was of interest to determine whether the underlying neural circuits that use glutamate as a neurotransmitter function normally in the prefrontal cortex of SHR. An in vitro superfusion technique was used to demonstrate that glutamate caused a concentration-dependent stimulation of [3H]norepinephrine release from rat prefrontal cortex slices. Glutamate (100 microM and 1 mM) caused significantly greater release of norepinephrine from prefrontal cortex slices of SHR than from control slices. The effect of glutamate was not mediated by NMDA receptors, since NMDA (10 and 100 microM) did not exert any effect on norepinephrine release and MK-801 (10 microM) did not antagonize the effect of 100 microM glutamate. These results demonstrate that glutamate stimulates norepinephrine release from rat prefrontal cortex slices and that this increase is enhanced in SHR. The results are consistent with the suggestion that the noradrenergic system is overactive in prefrontal cortex of SHR, the animal model for ADHD.

Gou-teng (from Uncaria rhynchophylla Miquel)-induced endothelium-dependent and -independent relaxations in the isolated rat aorta.

PubMed

Kuramochi, T; Chu, J; Suga, T

1994-01-01

Gou-teng is a drug used for treatment of hypertension in Chinese medicine. Its antihypertensive action has been previously confirmed in the spontaneously hypertensive rat (SHR). Here, its vasorelaxing effect and the mechanisms of actions were studied in vitro. Gou-teng extract (GTE) relaxed the norepinephrine (NE)-precontracted aortic ring preparations isolated from Wistar Kyoto rats (WKY) with and without intact endothelium; the latter was significantly less sensitive than the former. The GTE-induced endothelium-dependent relaxation was significantly inhibited by NG-monomethyl-L-arginine (NMMA) in a dose-dependent manner while indomethacin did not affect the relaxation. Atropine inhibited the acetylcholine (ACh)-induced endothelium-dependent relaxation but did not the GTE-induced one. Furthermore, once GTE was applied, the following NE-induced contraction was significantly reduced even after repeated washout. NMMA effectively reduced and rather reversed this residual effect of GTE. From these results, it is concluded that GTE relaxes the NE-precontracted rat aorta through endothelium-dependent and, to lesser extent, -independent mechanisms. The endothelium-dependent component would be mediated by EDRF/NO pathway in which the muscarinic cholinoceptors were not involved. Thus, GTE appears to be a potent and long-lasting vasodilator mainly through EDRF/NO release.

Aging Induces Changes in the Somatic Nerve and Postsynaptic Component without Any Alterations in Skeletal Muscles Morphology and Capacity to Carry Load of Wistar Rats

PubMed Central

Krause Neto, Walter; Silva, Wellington de Assis; Ciena, Adriano P.; de Souza, Romeu R.; Anaruma, Carlos A.; Gama, Eliane F.

2017-01-01

The present study aimed to analyze the morphology of the peripheral nerve, postsynaptic compartment, skeletal muscles and weight-bearing capacity of Wistar rats at specific ages. Twenty rats were divided into groups: 10 months-old (ADULT) and 24 months-old (OLD). After euthanasia, we prepared and analyzed the tibial nerve using transmission electron microscopy and the soleus and plantaris muscles for cytofluorescence and histochemistry. For the comparison of the results between groups we used dependent and independent Student's t-test with level of significance set at p ≤ 0.05. For the tibial nerve, the OLD group presented the following alterations compared to the ADULT group: larger area and diameter of both myelinated fibers and axons, smaller area occupied by myelinated and unmyelinated axons, lower numerical density of myelinated fibers, and fewer myelinated fibers with normal morphology. Both aged soleus and plantaris end-plate showed greater total perimeter, stained perimeter, total area and stained area compared to ADULT group (p < 0.05). Yet, aged soleus end-plate presented greater dispersion than ADULT samples (p < 0.05). For the morphology of soleus and plantaris muscles, density of the interstitial volume was greater in the OLD group (p < 0.05). No statistical difference was found between groups in the weight-bearing tests. The results of the present study demonstrated that the aging process induces changes in the peripheral nerve and postsynaptic compartment without any change in skeletal muscles and ability to carry load in Wistar rats. PMID:29326543

A Comparison of the Metalinguistic Performance and Spelling Development of Children With Inconsistent Speech Sound Disorder and Their Age-Matched and Reading-Matched Peers.

PubMed

McNeill, Brigid C; Wolter, Julie; Gillon, Gail T

2017-05-17

This study explored the specific nature of a spelling impairment in children with speech sound disorder (SSD) in relation to metalinguistic predictors of spelling development. The metalinguistic (phoneme, morphological, and orthographic awareness) and spelling development of 28 children ages 6-8 years with a history of inconsistent SSD were compared to those of their age-matched (n = 28) and reading-matched (n = 28) peers. Analysis of the literacy outcomes of children within the cohort with persistent (n = 18) versus resolved (n = 10) SSD was also conducted. The age-matched peers outperformed the SSD group on all measures. Children with SSD performed comparably to their reading-matched peers on metalinguistic measures but exhibited lower spelling scores. Children with persistent SSD generally had less favorable outcomes than children with resolved SSD; however, even children with resolved SSD performed poorly on normative spelling measures. Children with SSD have a specific difficulty with spelling that is not commensurate with their metalinguistic and reading ability. Although low metalinguistic awareness appears to inhibit these children's spelling development, other factors should be considered, such as nonverbal rehearsal during spelling attempts and motoric ability. Integration of speech-production and spelling-intervention goals is important to enhance literacy outcomes for this group.

Match running performance and skill execution improves with age but not the number of disposals in young Australian footballers.

PubMed

Gastin, Paul B; Tangalos, Christie; Torres, Lorena; Robertson, Sam

2017-12-01

This study investigated age-related differences in maturity, physical and functional characteristics and playing performance in youth Australian Football (AF). Young male players (n = 156) were recruited from 12 teams across 6 age groups (U10-U15) of a recreational AF club. All players were tested for body size, maturity and fitness. Player performance was assessed during a match in which disposals (kicks and handballs) and their effectiveness were coded from a video recording and match running performance measured using Global Positioning System. Significant main effects (P < 0.01) for age group were observed for age, years to peak height velocity, body mass, height, 20 m sprint, maximal speed over 20 m, vertical jump, 20 m multistage shuttle run, match distance, high-speed running distance, peak speed, number of effective disposals and percentage of effective disposals. Age-related differences in fitness characteristics (speed, lower body power and endurance) appeared to transfer to match running performance. The frequency in which players disposed of the football did not differ between age groups, however the effectiveness of each disposal (i.e., % effective disposals) improved with age. Match statistics, particularly those that evaluate skill execution outcome (i.e., effectiveness), are useful to assess performance and to track player development over time. Differences between age groups, and probably variability within age groups, are strongly associated with chronological age and maturity.

Differential gene expression in Schistosoma japonicum schistosomula from Wistar rats and BALB/c mice

PubMed Central

2011-01-01

Background More than 46 species of mammals can be naturally infected with Schistosoma japonicum in the mainland of China. Mice are permissive and may act as the definitive host of the life cycle. In contrast, rats are less susceptible to S. japonicum infection, and are considered to provide an unsuitable micro-environment for parasite growth and development. Since little is known of what effects this micro-environment has on the parasite itself, we have in the present study utilised a S. japonicum oligonucleotide microarray to compare the gene expression differences of 10-day-old schistosomula maintained in Wistar rats with those maintained in BALB/c mice. Results In total 3,468 schistosome genes were found to be differentially expressed, of which the majority (3,335) were down-regulated (≤ 2 fold) and 133 were up-regulated (≥ 2 fold) in schistosomula from Wistar rats compared with those from BALB/c mice. Gene ontology (GO) analysis revealed that of the differentially expressed genes with already established functions or close homology to well characterized genes in another organisms, many are related to important biological functions or molecular processes. Among the genes that were down-regulated in schistosomula from Wistar rats, some were associated with metabolism, signal transduction and development. Of these genes related to metabolic processes, areas including translation, protein and amino acid phosphorylation, proteolysis, oxidoreductase activities, catalytic activities and hydrolase activities, were represented. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis of differential expressed genes indicated that of the 328 genes that had a specific KEGG pathway annotation, 324 were down-regulated and were mainly associated with metabolism, growth, redox pathway, oxidative phosphorylation, the cell cycle, ubiquitin-mediated proteolysis, protein export and the MAPK (mitogen-activated protein kinases) signaling pathway. Conclusions This work

Evaluation of Cardiovascular Risk Factors in the Wistar Audiogenic Rat (WAR) Strain

PubMed Central

Fazan, Rubens; Silva, Carlos Alberto A.; Oliveira, José Antônio Cortes; Salgado, Helio Cesar; Montano, Nicola; Garcia-Cairasco, Norberto

2015-01-01

Introduction Risk factors for life-threatening cardiovascular events were evaluated in an experimental model of epilepsy, the Wistar Audiogenic Rat (WAR) strain. Methods We used long-term ECG recordings in conscious, one year old, WAR and Wistar control counterparts to evaluate spontaneous arrhythmias and heart rate variability, a tool to assess autonomic cardiac control. Ventricular function was also evaluated using the pressure-volume conductance system in anesthetized rats. Results Basal RR interval (RRi) was similar between WAR and Wistar rats (188±5 vs 199±6 ms). RRi variability strongly suggests that WAR present an autonomic imbalance with sympathetic overactivity, which is an isolated risk factor for cardiovascular events. Anesthetized WAR showed lower arterial pressure (92±3 vs 115±5 mmHg) and exhibited indices of systolic dysfunction, such as higher ventricle end-diastolic pressure (9.2±0.6 vs 5.6±1 mmHg) and volume (137±9 vs 68±9 μL) as well as lower rate of increase in ventricular pressure (5266±602 vs 7320±538 mmHg.s-1). Indices of diastolic cardiac function, such as lower rate of decrease in ventricular pressure (-5014±780 vs -7766±998 mmHg.s-1) and a higher slope of the linear relationship between end-diastolic pressure and volume (0.078±0.011 vs 0.036±0.011 mmHg.μL), were also found in WAR as compared to Wistar control rats. Moreover, Wistar rats had 3 to 6 ventricular ectopic beats, whereas WAR showed 15 to 30 ectopic beats out of the 20,000 beats analyzed in each rat. Conclusions The autonomic imbalance observed previously at younger age is also present in aged WAR and, additionally, a cardiac dysfunction was also observed in the rats. These findings make this experimental model of epilepsy a valuable tool to study risk factors for cardiovascular events in epilepsy. PMID:26029918

Dihydroquercetin Does Not Affect Age-Dependent Increase in Blood Pressure and Angiotensin-Converting Enzyme Activity in the Aorta of Hypertensive Rats.

PubMed

Slashcheva, G A; Rykov, V A; Lobanov, A V; Murashev, A N; Kim, Yu A; Arutyunyan, T V; Korystova, A F; Kublik, L N; Levitman, M Kh; Shaposhnikona, V V; Korystov, Yu N

2016-09-01

We analyzed changes in angiotensin-converting enzyme activity in the aorta of hypertensive SHR rats against the background of age-related BP increase (from week 7 to 14) and the effect of dihydroquercetin on BP rise and angiotensin-converting enzyme activity. Normotensive WKY rats of the same age were used as the control. BP and activity of angiotensin-converting enzyme in the aorta of SHR rats increased with age. Dihydroquercetin in doses of 100 and 300 μg/kg per day had no effect on the increase of these parameters; dihydroquercetin administered to 14-week-old WKY rats in a dose of 300 μg/kg reduced activity of the angiotensin-converting enzyme. Thus, the early (7-14 weeks) increase in BP and angiotensin-converting enzyme activity in the aorta of SHR rats was not modified by flavonoids (dihydroquercetin) in contrast to other rat strains and humans, which is indicative of specificity of hypertension mechanism in SHR rats.

Effects of nimodipine on learning in normotensive and spontaneously hypertensive rats.

PubMed

Meneses, A; Terrón, J A; Ibarra, M; Hong, E

1997-04-01

It is well known that the calcium channel blocker, nimodipine, has beneficial effects on learning in either aged or hypertensive animals and humans. However, no attempts have been made to investigate if nimodipine can reverse the synergistic deleterious effects of aging and hypertension in the same subject. Therefore, this study investigated the effects of stable infusions of nimodipine in the autoshaping learning task using middle-aged normotensive (WKY) and hypertensive (SHR) rats. WKY and SHR of 12 months of age were implanted with osmotic minipumps releasing either vehicle or nimodipine (0.4 mg/kg/day). After 3 weeks of treatment, the animals received autoshaping training sessions during 4 consecutive days. The WKY animals treated with nimodipine exhibited the highest levels of learning during the last session, the rank order being WKY-nimodipine > SHR-nimodipine > WKY-vehicle > SHR-vehicle. These results confirm that nimodipine can reverse the impairing effects of either aging or hypertension on learning; the presence of both conditions, however, might produce more severe dysfunctional changes that cannot be totally reversed by nimodipine.

In Brief: Kyoto Protocol moves forward

NASA Astrophysics Data System (ADS)

Showstack, Randy

2004-10-01

The Russian cabinet's 30 September endorsement of the Kyoto Protocol to the United Nations Framework Convention on Climate Change (UNFCCC) likely clears the way for the treaty's ratification by that country's parliament and for its entry into force. The protocol enters into force when not less than 55 Parties to the Convention, including industrialized countries (so called ``Annex I Parties'') which accounted in total for at least 55 % of the total carbon dioxide emissions for 1990 from that group, officially have agreed to the treaty.

Aging and Haptic-Visual Solid Shape Matching.

PubMed

Norman, J Farley; Adkins, Olivia C; Dowell, Catherine J; Hoyng, Stevie C; Gilliam, Ashley N; Pedersen, Lauren E

2017-08-01

A total of 36 younger (mean age = 21.3 years) and older adults (mean age = 73.8 years) haptically explored plastic copies of naturally shaped objects (bell peppers, Capsicum annuum) one at a time for 7 s each. The participants' task was to then choose which of 12 concurrently visible objects had the same solid shape as the one they felt. The younger and older participants explored the object shapes using either one, three, or five fingers (there were six participants for each combination of number of fingers and age group). The outcome was different from that of previous research conducted with manmade objects. Unlike Jansson and Monaci (2006) , we found that for most objects, our participants' performance was unaffected by variations in the number of fingers used for haptic exploration. While there was no significant overall effect of the number of fingers, there was a significant main effect of age. The younger adults' shape matching performance was 48.6% higher than that of the older adults. When perceiving naturally shaped objects such as bell peppers, it appears that the usage of a single finger can be as effective as haptic exploration with a whole complement of five fingers.

Degenerative changes in adolescent spines: a comparison of motocross racers and age-matched controls.

PubMed

Daniels, David J; Luo, T David; Puffer, Ross; McIntosh, Amy L; Larson, A Noelle; Wetjen, Nicholas M; Clarke, Michelle J

2015-03-01

Motocross racing is a popular sport; however, its impact on the growing/developing pediatric spine is unknown. Using a retrospective cohort model, the authors compared the degree of advanced degenerative findings in young motocross racers with findings in age-matched controls. Patients who had been treated for motocross-related injury at the authors' institution between 2000 and 2007 and had been under 18 years of age at the time of injury and had undergone plain radiographic or CT examination of any spinal region were eligible for inclusion. Imaging was reviewed in a blinded fashion by 3 physicians for degenerative findings, including endplate abnormalities, loss of vertebral body height, wedging, and malalignment. Acute pathological segments were excluded. Spine radiographs from age-matched controls were similarly reviewed and the findings were compared. The motocross cohort consisted of 29 riders (mean age 14.7 years; 82% male); the control cohort consisted of 45 adolescents (mean age 14.3 years; 71% male). In the cervical spine, the motocross cohort had 55 abnormalities in 203 segments (average 1.90 abnormalities/patient) compared with 20 abnormalities in 213 segments in the controls (average 0.65/patient) (p = 0.006, Student t-test). In the thoracic spine, the motocross riders had 51 abnormalities in 292 segments (average 2.04 abnormalities/patient) compared with 25 abnormalities in 299 segments in the controls (average 1.00/patient) (p = 0.045). In the lumbar spine, the motocross cohort had 11 abnormalities in 123 segments (average 0.44 abnormalities/patient) compared with 15 abnormalities in 150 segments in the controls (average 0.50/patient) (p = 0.197). Increased degenerative changes in the cervical and thoracic spine were identified in adolescent motocross racers compared with age-matched controls. The long-term consequences of these changes are unknown; however, athletes and parents should be counseled accordingly about participation in motocross

Deficient prepulse inhibition of acoustic startle in Hooded-Wistar rats compared with Sprague-Dawley rats.

PubMed

van den Buuse, Maarten

2003-04-01

1. Prepulse inhibition of acoustic startle has been suggested as a model of sensorimotor gating and central sensory information processing. Prepulse inhibition is impaired in patients with schizophrenia and responses can be restored by antipsychotic drug treatment. In the present study, startle and prepulse inhibition of startle were compared in different rat strains. 2. Sprague-Dawley rats showed robust inhibition of startle responses by increasing intensities of prepulse delivered just before the startle stimulus. In contrast, at both 4 and 10 weeks of age, rats of the Hooded-Wistar line had markedly reduced prepulse inhibition, although startle responses were not different. 3. Treatment with the dopamine receptor agonist apomorphine (0.1 mg/kg) or the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 (0.1 mg/kg) caused disruption of prepulse inhibition in Sprague-Dawley rats. In Hooded-Wistar rats, apomorphine further reduced the already low level of prepulse inhibition, but MK-801 treatment had no significant effect. This suggests that the impaired prepulse inhibition in Hooded-Wistar rats could be caused by changes in glutamatergic activity and/or NMDA receptors in these rats. 4. In photocell cages, spontaneous exploratory activity and inner zone activity were significantly lower in Hooded-Wistar rats than in Sprague-Dawley rats. Similarly, on the elevated plus-maze, Hooded-Wistar rats showed a lower propensity to visit the open arms. In contrast, amphetamine (0.5 mg/kg)-induced locomotor hyperactivity, an animal model of psychosis, was enhanced in Hooded-Wistar rats. 5. These data suggest that the Hooded-Wistar line could be a useful genetic animal model to study the interaction of glutamatergic and dopaminergic mechanisms in anxiety and schizophrenia.

Endogenous Melanocortin System Activity Contributes to the Elevated Arterial Pressure in Spontaneously Hypertensive Rats

PubMed Central

da Silva, Alexandre A.; do Carmo, Jussara M.; Kanyicska, Bela; Dubinion, John; Brandon, Elizabeth; Hall, John E.

2009-01-01

Previous studies suggest that activation of the CNS melanocortin system reduces appetite while increasing sympathetic activity and arterial pressure. The present study tested whether endogenous activity of the CNS melanocortin 3/4 receptors (MC3/4-R) contributes to elevated arterial pressure in the spontaneously hypertensive rat (SHR), a model of hypertension with increased sympathetic activity. A cannula was placed in the lateral ventricle of male SHR and Wistar (WKY) rats for chronic intracerebroventricular (ICV) infusions (0.5 μL/h). Mean arterial pressure (MAP) and heart rate (HR) were recorded 24 hour/d using telemetry. After 5-day control period, rats were infused with MC3/4-R antagonist (SHU-9119, 1 nmol/h-ICV) for 12 days, followed by 5-day posttreatment period. MC3/4-R antagonism increased food intake in SHR by 90% and in WKY by 125%, resulting in marked weight gain, insulin resistance, and hyperleptinemia in SHR and WKY. Despite weight gain, MC3/4-R antagonism reduced HR in SHR and WKY (≈40 bpm), while lowering MAP to a greater extent in SHR (−22±4 mm Hg) than WKY (−4±3 mm Hg). SHU9119 treatment failed to cause further reductions in MAP during chronic adrenergic blockade with propranolol and terazosin. These results suggest that endogenous activity of the CNS melanocortin system contributes to the maintenance of adrenergic tone and elevated arterial pressure in SHR even though mRNA levels for POMC and MC4R in the mediobasal hypothalamus were not increased compared to WKY. These results also support the hypothesis that weight gain does not raise arterial pressure in the absence of a functional MC3/4-R. PMID:18285617

Considering WTO law in the design of climate change regimes beyond Kyoto

NASA Astrophysics Data System (ADS)

Gaines, Sanford E.

2009-11-01

This article describes the most important provisions of World Trade Organization (WTO) agreements that should be considered in designing laws and regulations under likely post-Kyoto climate change mitigation regimes. The Kyoto Protocol and the expected post-Kyoto international climate agreement depend on national measures to implement market-based mitigation measures. This market strategy promotes international exchanges of goods, investments, and services such as cross-border trading of credits for emissions reductions and transnational financing for projects that avoid emissions through the Clean Development Mechanism. Moreover, the United States and other countries, concerned over "leakage" of greenhouse gas (GHG) emissions through relocation of industry to other countries coupled with political worry over manufacturing competitiveness, have proposed national climate legislation containing border adjustments on imported goods or implicit subsidies for national producers, raising additional WTO considerations. The article assesses the likely effectiveness of such trade-related measures in achieving climate change mitigation goals and the potential trade policy infringements and trade distortions that they might bring about. Alternative strategies for achieving GHG mitigation goals in closer conformity with WTO law and policy will be suggested.

Treadmill running prevents age-related memory deficit and alters neurotrophic factors and oxidative damage in the hippocampus of Wistar rats.

PubMed

Vanzella, Cláudia; Neves, Juliana Dalibor; Vizuete, Adriana Fernanda; Aristimunha, Dirceu; Kolling, Janaína; Longoni, Aline; Gonçalves, Carlos Alberto Saraiva; Wyse, Angela T S; Netto, Carlos Alexandre

2017-09-15

Clinical and pre-clinical studies indicate that exercise is beneficial to many aspects of brain function especially during aging. The present study investigated the effects of a treadmill running protocol in young (3month-old) and aged (22month-old) male Wistar rats, on: I) cognitive function, as assessed by spatial reference memory in the Morris water maze; II) oxidative stress parameters and the expression of neurotrophic factors BDNF, NT-3, IGF-1 and VEGF in the hippocampus. Animals of both ages were assigned to sedentary (non-exercised) and exercised (20min of daily running sessions, 3 times per week for 4weeks) groups. Cognition was assessed by a reference memory task run in the Morris water maze; twenty four hours after last session of behavioral testing hippocampi were collected for biochemical analysis. Results demonstrate that the moderate treadmill running exercise: I) prevented age-related deficits in reference memory in the Morris water maze; II) prevented the age-related increase of reactive oxygen species levels and lipid peroxidation in the hippocampus; III) caused an increase of BDNF, NT-3 and IGF-1 expression in the hippocampus of aged rats. Taken together, results suggest that both exercise molecular effects, namely the reduction of oxidative stress and the increase of neurotrophic factors expression in the hippocampus, might be related to its positive effect on memory performance in aged rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic administration of thiamine pyrophosphate decreases age-related histological atrophic testicular changes and improves sexual behavior in male Wistar rats.

PubMed

Hernández-Montiel, H L; Vásquez López, C M; González-Loyola, J G; Vega-Anaya, G C; Villagrán-Herrera, M E; Gallegos-Corona, M A; Saldaña, C; Ramos Gómez, M; García Horshman, P; García Solís, P; Solís-S, J C; Robles-Osorio, M L; Ávila Morales, J; Varela-Echavarría, A; Paredes Guerrero, R

2014-06-01

Aging is a multifactorial universal process and constitutes the most important risk factor for chronic-degenerative diseases. Although it is a natural process, pathological aging arises when these changes occur quickly and the body is not able to adapt. This is often associated with the generation of reactive oxygen species (ROS), inflammation, and a decrease in the endogenous antioxidant systems, constituting a physiopathological state commonly found in chronic-degenerative diseases. At the testicular level, aging is associated with tissue atrophy, decreased steroidogenesis and spermatogenesis, and sexual behavior disorders. This situation, in addition to the elevated generation of ROS in the testicular steroidogenesis, provides a critical cellular environment causing oxidative damage at diverse cellular levels. To assess the effects of a reduction in the levels of ROS, thiamine pyrophosphate (TPP) was chronically administered in senile Wistar rats. TPP causes an activation of intermediate metabolism routes, enhancing cellular respiration and decreasing the generation of ROS. Our results show an overall decrease of atrophic histological changes linked to aging, with higher levels of serum testosterone, sexual activity, and an increase in the levels of endogenous antioxidant enzymes in TPP-treated animals. These results suggest that TPP chronic administration decreases the progression of age-related atrophic changes by improving the intermediate metabolism, and by increasing the levels of antioxidant enzymes.

Fibronectin type III domain containing 5 attenuates NLRP3 inflammasome activation and phenotypic transformation of adventitial fibroblasts in spontaneously hypertensive rats.

PubMed

Ling, Li; Chen, Dan; Tong, Ying; Zang, Ying-Hao; Ren, Xing-Sheng; Zhou, Hong; Qi, Xiao-Hong; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

2018-05-01

Phenotypic transformation of adventitial fibroblasts is important in the pathogenesis of hypertension. This study was designed to determine whether fibronectin type III domain containing 5 (FNDC5) alleviates the phenotypic transformation of adventitial fibroblasts in hypertension and the underlying mechanisms. Experiments were carried out in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and primary aortic adventitial fibroblasts. FNDC5 was downregulated and NLRP3 inflammasome was activated in aortic adventitia of SHR. FNDC5 overexpression attenuated adventitial fibroblasts phenotypic transformation, excessive synthesis and secretion of matrix components, NLRP3 inflammasome activation and inflammation in adventitial fibroblasts from SHR. Moreover, FNDC5 overexpression reduced NADPH oxidase 2 (NOX2) expression and reactive oxygen species (ROS) production in adventitial fibroblasts from SHR. Similarly, exogenous FNDC5 inhibited adventitial fibroblasts phenotypic transformation, expression of matrix components, NLRP3 inflammasome activation and NOX2 expression in adventitial fibroblasts from SHR. FNDC5 overexpression in rats attenuated phenotypic transformation, inflammation and reactive oxygen species (ROS) production in the aortic adventitia of SHR. Furthermore, FNDC5 overexpression reduced blood pressure and alleviated vascular remodeling in SHR. FNDC5 reduces NOX2-derived ROS production, NLRP3 inflammasome activation and phenotypic transformation in adventitial fibroblasts of SHR. FNDC5 plays a beneficial role in attenuating vascular inflammation, vascular remodeling and hypertension in SHR.

Atrial natriuretic peptide regulation of noradrenaline release in the anterior hypothalamic area of spontaneously hypertensive rats.

PubMed Central

Peng, N; Oparil, S; Meng, Q C; Wyss, J M

1996-01-01

In spontaneously hypertensive rats (SHR), high NaCl diets increase arterial pressure and sympathetic nervous system activity by decreasing noradrenaline release in the anterior hypothalamic area (AHA), thereby reducing the activation of sympathoinhibitory neurons in AHA. Atrial natriuretic peptide (ANP) can inhibit the release of noradrenaline, and ANP concentration is elevated in the AHA of SHR. The present study tests the hypothesis that in SHR, local ANP inhibits noradrenaline release from nerve terminals in AHA. Male SHR fed a basal or high NaCl diet for 2 wk and normotensive Wistar Kyoto rats (WKY) fed a basal NaCl diet were studied. In SHR on the basal diet, microperfusion of exogenous ANP into the AHA elicited a dose-related decrease in the concentration of the major noradrenaline metabolite 3-methoxy-4-hydroxy-phenylglycol (MOPEG) in the AHA; this effect was attenuated in the other two groups. In a subsequent study, the ANP-C (clearance) receptor agonist c-ANP was microperfused into the AHA to increase extracellular concentration of endogenous ANP in AHA. c-ANP reduced AHA MOPEG concentration in SHR on the basal NaCl diet but not in the other two groups. These data support the hypothesis that local ANP inhibits noradrenaline release in the AHA and thereby contributes to NaCl-sensitive hypertension in SHR. PMID:8903325

Chronic social stress increases nitric oxide-dependent vasorelaxation in normotensive rats

PubMed Central

Puzserova, Angelika; Bernatova, Iveta

2010-01-01

The aim of this study was to examine oxidative load and endothelium-dependent vasorelaxation in the serotonin pre-constricted femoral artery (FA) of Wistar-Kyoto (WKY) rats exposed to chronic social stress produced by crowding in the presence or absence of ascorbic acid (AsA) in working solution. Adult male rats were randomly divided into control (living space: 480 cm2/rat) or stressed (living space: 200 cm2/rat) groups for 8 weeks. Blood pressure and heart rate, determined using tail-cuff plethysmography, were not influenced by stress vs. control. Conjugated dienes (CD) and concentrations of thiobarbituric acid-reactive substances (TBARS) were measured in the left ventricle and liver (for assessment of oxidative load) and were found unchanged by chronic crowding. The nitric oxide (NO)-dependent component of endothelium-dependent relaxation was investigated in the FA using a wire myograph. In both the presence and absence of AsA, acetylcholine-induced relaxation of the FA of stressed rats significantly exceeded that of the controls, which was associated with an increase of the NO-dependent component. In conclusion, the data showed that chronic crowding did not produce oxidative stress in the organs investigated and indicate that elevation of NO production during chronic stress is an important way of adaptation, which may prevent normotensive rats from the development of stress-induced hypertension. PMID:21331175

Effects of aging and gender on micro-rheology of blood in 3 to 18 months old male and female Wistar (Crl:WI) rats.

PubMed

Somogyi, Viktoria; Peto, Katalin; Deak, Adam; Tanczos, Bence; Nemeth, Norbert

2018-01-01

Age- and gender-related alterations of hemorheological parameters have not been completely elucidated to date. Experiments on older animals may give valuable information on this issue. However, the majority of rheological studies have been performed in young rodents. We aimed to investigate the influence of aging and gender on hemorheological parameters in rats. Coeval male (n=10) and female (n=10) Wistar (Crl:WI) rats were followed-up over 15 months. Blood samples were obtained from the lateral tail vein at 3, 4, 5, 9, 12, 15 and 18 months of age. Hematological parameters, red blood cell deformability (elongation under shear), osmotic gradient deformability and erythrocyte aggregation were tested. Body weight and the estrus cycle (in females) were also examined. Erythrocyte aggregation showed age- and gender-related variations. Red blood cell deformability was greater in females and gradually decreased over the 15-month period in both genders. Erythrocyte aggregation was greater in male rats at most ages, but did not show consistent changes with age. The micro-rheological parameters showed age-related alterations with gender differences. The effect of the estrous cycle cannot be excluded in female rats. The results provide reference data for studies of aging in rats and of the mechanism related to age and gender differences in hemorheology.

Dynamic molecular imaging of cardiac innervation using a dual headpinhole SPECT system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Jicun; Boutchko, Rostyslav; Sitek, Arkadiusz

2008-03-29

Typically 123I-MIBG is used for the study of innervation andfunction of the sympathetic nervous system in heart failure. The protocolinvolves two studies: first a planar or SPECT scan is performed tomeasure initial uptake of the tracer, followed some 3-4 hours later byanother study measuring the wash-out of the tracer from the heart. A fastwash-out is indicative of a compromised heart. In this work, a dual headpinhole SPECT system was used for imaging the distribution and kineticsof 123I-MIBG in the myocardium of spontaneous hypertensive rats (SHR) andnormotensive Wistar Kyoto (WKY) rats. The system geometry was calibratedbased on a nonlinear point projectionmore » fitting method using a three-pointsource phantom. The angle variation effect of the parameters was modeledwith a sinusoidal function. A dynamic acquisition was performed byinjecting 123I-MIBG into rats immediately after starting the dataacquisition. The detectors rotated continuously performing a 360o dataacquisition every 90 seconds. We applied the factor analysis (FA)methodand region of interest (ROI) sampling method to obtain time activitycurves (TACs)in the blood pool and myocardium and then appliedtwo-compartment modeling to estimate the kinetic parameters. Since theinitial injection bolus is too fast for obtaining a consistenttomographic data set in the first few minutes of the study, we appliedthe FA method directly to projections during the first rotation. Then thetime active curves for blood and myocardial tissue were obtained from ROIsampling. The method was applied to determine if there were differencesin the kinetics between SHR and WKY rats and requires less time byreplacing the delayed scan at 3-4 hours after injection with a dynamicacquisition over 90 to 120 minutes. The results of a faster washout and asmaller distribution volume of 123IMIBG near the end of life in the SHRmodel of hypertrophic cardiomyopthy may be indicative of a failing heartin late stages of heart failure.« less

Prostatic relaxation induced by agmatine is decreased in spontaneously hypertensive rats.

PubMed

Lee, Liang-Ming; Tsai, Tsung-Chin; Chung, Hsien-Hui; Tong, Yat-Ching; Cheng, Juei-Tang

2012-09-01

What's known on the subject? and What does the study add? Neurotransmitters are known to control prostate contractility. Agmatine is one of them and induces relaxation through imidazoline receptors. The paper shows that the action of agmatine is reduced in hypertensive rats, and that this change is related to the decrease of ATP-sensitive potassium channels in the prostate. The findings can increase our understanding of the possible underlying mechanism for the development of clinical benign prostatic hyperplasia. To compare agmatine-induced prostatic relaxation in hypertensive and control rats. To investigate the responsible mechanism(s) and the role of the ATP-sensitive potassium channel. Prostate strips were isolated from male spontaneously hypertensive (SH) rats and normal Wistar-Kyoto (WKY) rats for measurement of isometric tension. The strips were precontracted with 1 µmol/L phenylephrine or 50 mmol/L KCl. Dose-dependent relaxation of the prostatic strips was studied by cumulative administration of agmatine, 1 to 100 µmol/L, into the organ bath. Effects of specific antagonists on agmatine-induced relaxation were studied. Western blotting analysis was used to measure the gene expression of the ATP-sensitive potassium channel in the rat prostate. Prostatic relaxation induced by agmatine was markedly reduced in SH rats compared with WKY rats. The relaxation caused by agmatine was abolished by BU224, a selective imidazoline I(2)-receptor antagonist, but was not modified by efaroxan at a dose sufficient to block imidazoline I(1)-receptors. The relaxation induced by diazoxide at a concentration sufficient to activate ATP-sensitive potassium channels was markedly reduced in the SH rat prostate. Expressions of ATP-sensitive potassium channel sulphonylurea receptor and inwardly rectifying potassium channel (Kir) 6.2 subunits were both decreased in the prostate of SH rats. The decrease of agmatine-induced prostatic relaxation in SH rats is related to the change in

[Dr. Michiharu Matsuoka, founder of the Department of Orthopaedic Surgery, Kyoto University, and his achievements. Part 4: Prof. M. Matsuoka's lecture to medical and civic communities].

PubMed

Hirotani, Hayato

2010-03-01

Dr. M. Matsuoka gave many lectures to physicians at the Postdoctoral Course Lectures sponsored by the Kyoto Eisei Kensasho (Kyoto Bacterial and Biochemical Laboratory) run by the Kyoto Medical Association, and the Postdoctoral Course Lectures of the Kyoto Medical School, Kyoto Imperial University. He was also invited to give lectures at several regional medical associations. He also was a speaker at the Kyoto Imperial University Extension course and he lectured at the Enryakuji Temple on Mt. Hiei, sponsored by a newspaper company. It is remarkable that these activities were carried out in addition to his other notable academic work previously reported.

[Beginnings of the study of Western sciences, "Rangaku," in Kyoto and Osaka in close relations with the Edo school].

PubMed

Murata, T

2001-01-01

Beginnings of the study of Western sciences, "Rangaku," in Kyoto and Osaka in the late 18th century are reviewed. Profiles and achievements of several active learners are briefly described; they include Koishi Genzui (Osaka-Kyoto), Tsuji Ranshitsu (Kyoto), Kimura Kenkadō (Osaka), and Hashimoto Sōkichi (Osaka). Genzui, after having successfully made good relations with Sugita Genpaku and Ohtsuki Gentaku, leading masters of the Edo school, played a role of an advocator for promoting "Rangaku" in Osaka and Kyoto. As a result, Kenkadō attained the publication of his book "Ikkaku Sankō," a monograph of the Western crude drug unicorn, with the help of Gentaku, who had translated a Dutch reference into Japanese for him. Ranshitsu and Sōkichi were taught the Dutch language by Gentaku; Sōkichi is known as the founder of "Rangaku" in Osaka.

Comparison of brachial artery vasoreactivity in elite power athletes and age-matched controls.

PubMed

Welsch, Michael A; Blalock, Paul; Credeur, Daniel P; Parish, Tracie R

2013-01-01

Elite endurance athletes typically have larger arteries contributing to greater skeletal muscle blood flow, oxygen and nutrient delivery and improved physical performance. Few studies have examined structural and functional properties of arteries in power athletes. To compare the size and vasoreactivity of the brachial artery of elite power athletes to age-matched controls. It was hypothesized brachial artery diameters of athletes would be larger, have less vasodilation in response to cuff occlusion, but more constriction after a cold pressor test than age-matched controls. Eight elite power athletes (age = 23 ± 2 years) and ten controls (age = 22 ± 1 yrs) were studied. High-resolution ultrasonography was used to assess brachial artery diameters at rest and following 5 minutes of forearm occlusion (Brachial Artery Flow Mediated Dilation = BAFMD) and a cold pressor test (CPT). Basic fitness measures included a handgrip test and 3-minute step test. Brachial arteries of athletes were larger (Athletes 5.39 ± 1.51 vs. 3.73 ± 0.71 mm, p<0.05), had greater vasodilatory (BAFMD%: Athletes: 8.21 ± 1.78 vs. 5.69 ± 1.56%) and constrictor (CPT %: Athletes: -2.95 ± 1.07 vs. -1.20 ± 0.48%) responses, compared to controls. Vascular operating range (VOR = Peak dilation+Peak Constriction) was also greater in athletes (VOR: Athletes: 0.55 ± 0.15 vs. 0.25 ± 0.18 mm, p<0.05). Athletes had superior handgrip strength (Athletes: 55.92 ± 17.06 vs. 36.77 ± 17.06 kg, p<0.05) but similar heart rate responses at peak (Athletes: 123 ± 16 vs. 130 ± 25 bpm, p>0.05) and 1 minute recovery (Athletes: 88 ± 21 vs. 98 ± 26 bpm, p>0.05) following the step test. Elite power athletes have larger brachial arteries, and greater vasoreactivity (greater vasodilatory and constrictor responses) than age-matched controls, contributing to a significantly greater VOR. These data extend the existence of an 'athlete's artery' as previously shown for elite endurance athletes to elite power athletes

Effects of age and spa treatment on match running performance over two consecutive games in highly trained young soccer players.

PubMed

Buchheit, Martin; Horobeanu, Cosmin; Mendez-Villanueva, Alberto; Simpson, Ben M; Bourdon, Pitre C

2011-03-01

The aim of this study was to examine the effect of age and spa treatment (i.e. combined sauna, cold water immersion, and jacuzzi) on match running performance over two consecutive matches in highly trained young soccer players. Fifteen pre- (age 12.8 ± 0.6 years) and 13 post- (15.9 ± 1 y) peak height velocity (PHV) players played two matches (Matches 1 and 2) within 48 h against the same opposition, with no specific between-match recovery intervention (control). Five post-PHV players also completed another set of two consecutive matches, with spa treatment implemented after the first match. Match running performance was assessed using a global positioning system with very-high-intensity running (> 16.1-19.0 km · h(-1)), sprinting distance (>19 km · h(-1)), and peak match speed determined. Match 2 very-high-intensity running was "possibly" impaired in post-PHV players (-9 ± 33%; ± 90% confidence limits), whereas it was "very likely" improved for the pre-PHV players (+27 ± 22%). The spa treatment had a beneficial impact on Match 2 running performance, with a "likely" rating for sprinting distance (+30 ± 67%) and "almost certain" for peak match speed (+6.4 ± 3%). The results suggest that spa treatment is an effective recovery intervention for post-PHV players, while its value in pre-PHV players is questionable.

Medial versus anterior open reduction for developmental hip dislocation in age-matched patients.

PubMed

Hoellwarth, Jason S; Kim, Young-Jo; Millis, Michael B; Kasser, James R; Zurakowski, David; Matheney, Travis H

2015-01-01

The difference between medial (MAOR) and anterior (AAOR) approaches for open reduction of developmental hip dysplasia in terms of risk for avascular necrosis (AVN) and need for further corrective surgery (FCS, femoral and/or acetabular osteotomy) is unclear. This study compared age-matched cohorts undergoing either MAOR or AAOR in terms of these 2 primary outcomes. Prognostic impact of presence of ossific nucleus at time of open reduction was also investigated. Institutional review board approval was obtained. Nineteen hips (14 patients) managed by MAOR were matched with 19 hips (18 patients) managed by AAOR based on age at operation (mean 6.0; range, 1.4 to 14.9 mo). Patients with neuromuscular conditions and known connective tissue disorders were excluded. Primary outcomes assessed at minimum 2 years' follow-up included radiographic evidence of AVN (Kalamchi and MacEwen) or requiring FCS. MAOR and AAOR cohorts were similar regarding age at open reduction, sex, laterality, and follow-up duration. One hip in each group had AVN before open reduction thus were excluded from AVN analysis. At minimum 2 years postoperatively (mean 6.2; range, 1.8 to 11.7 y), 4/18 (22%) MAOR and 5/18 (28%) AAOR met the same criteria for AVN (P=1.0). No predictors of AVN could be identified by regression analysis. Presence of an ossific nucleus preoperatively was not a protective factor from AVN (P=0.27). FCS was required in 4/19 (21%) MAOR and 7/19 (37%) AAOR hips (P=0.48). However, 7/12 (54%) hips failing closed reduction required FCS compared with 4/26 (16%) hips without prior failed closed reduction (P=0.024). Cox regression analysis showed that patients who failed closed reduction had an annual risk of requiring FCS approximately 6 times that of patients without a history of failed closed reduction (hazard ratio=6.1; 95% CI, 1.5-24.4; P=0.009), independent of surgical approach (P=0.55) or length of follow-up (P=0.78). In this study of age-matched patients undergoing either MAOR or

An iron-deficient diet during development induces oxidative stress in relation to age and gender in Wistar rats.

PubMed

Vieyra-Reyes, Patricia; Millán-Aldaco, Diana; Palomero-Rivero, Marcela; Jiménez-Garcés, Clementina; Hernández-González, Margarita; Caballero-Villarraso, Javier

2017-02-01

Iron is a trace element and a structural part of antioxidant enzymes, and its requirements vary according to age and gender. We hypothesized that iron deficiency (ID) leads to an increase in free radicals which mainly affect the brain, and the severity of damage would therefore be dependent on age and gender. Two groups of Wistar rats were evaluated evolutionarily: 100 rats (50 males; 50 females) with ID diet and 100 rats (50 males; 50 females) with standard diet. Both groups were offspring from mothers who were previously under the same dietary intervention. The ages studied roughly correspond to stages of human development: birth (0 postnatal day "PND" in rats), childhood (21 PND), early adolescence (42 PND), late adolescence (56 PND), and adulthood (70 PND). The following biomarkers in the brain, blood, and liver were analyzed: lipid peroxidation products (LPO), protein carbonyl content and activity of the antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. It was demonstrated that ID subjects are born with high levels of LPO in the brain and low antioxidant activity, the damage being more severe in males. After birth, antioxidant defense focuses on the central level (brain) in ID females and on the peripheral level (blood and liver) in ID males. In two critical stages of development, birth and late adolescence, antioxidant protection is insufficient to counteract oxidative damage in ID subjects. Moreover, we observed that the variability of results in the literature on oxidative stress and ID comes from gender and age of the subjects under study. With this, we can establish patterns and exact moments to carry out studies or treatments.

Effect of Paullinia cupana Mart. Commercial Extract During the Aging of Middle Age Wistar Rats: Differential Effects on the Hippocampus and Striatum.

PubMed

Mingori, Moara Rodrigues; Heimfarth, Luana; Ferreira, Charles Francisco; Gomes, Henrique Mautone; Moresco, Karla Suzana; Delgado, Jeferson; Roncato, Sabrina; Zeidán-Chuliá, Fares; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

2017-08-01

During aging, there is a marked decline in the antioxidant capacity of brain tissue, leading to a gradual loss of the antioxidant/oxidant balance, which causes oxidative damage. The effects of Paullinia cupana Mart. extract, which is described as being rich in caffeine and many polyphenol compounds, on the central nervous system have not been extensively investigated. The aim of this study was to therefore investigate the effect of a commercial guarana extract (CGE) on cognitive function, oxidative stress, and brain homeostasis proteins related to cognitive injury and senescence in middle age, male Wistar rats. Animals were randomly assigned to a group according to their treatment (saline, CGE, or caffeine). Solutions were administered daily by oral gavage for 6 months. Open field and novel object recognition tasks were performed before and after treatment. Biochemical analyses were carried out on the hippocampus and striatum. Our open field data showed an increase in exploratory activity and a decrease in anxiety-like behavior with caffeine but not with the CGE treatment. In the CGE-treated group, catalase activity decreased in the hippocampus and increased in the striatum. Analyses of the hippocampus and striatum indicate that CGE and/or caffeine altered some of the analyzed parameters in a tissue-specific manner. Our data suggest that CGE intake does not improve cognitive development, but modifies the oxidative stress machinery and neurodegenerative-signaling pathway, inhibiting pro-survival pathway molecules in the hippocampus and striatum. This may contribute to the development of unfavorable microenvironments in the brain and neurodegenerative disorders.

The Stereotype-Matching Effect: Greater Influence on Functioning When Age Stereotypes Correspond to Outcomes

PubMed Central

Levy, Becca R.; Leifheit-Limson, Erica

2009-01-01

Older individuals assimilate, and are targeted by, contradictory positive and negative age stereotypes. It was unknown whether the influence of stereotype valence is stronger when the stereotype content corresponds to the outcome domain. We randomly assigned older individuals to either positive-cognitive, negative-cognitive, positive-physical, or negative-physical subliminal-age-stereotype groups and assessed cognitive and physical outcomes. As predicted, when the age stereotypes corresponded to the outcome domains, their valence had a significantly greater impact on cognitive and physical performance. This suggests that if a match occurs, it is more likely to generate expectations that become self-fulfilling prophecies. PMID:19290757

The Fears, Phobias and Anxieties of Children with Autism Spectrum Disorders and Down Syndrome: Comparisons with Developmentally and Chronologically Age Matched Children

ERIC Educational Resources Information Center

Evans, David W.; Canavera, Kristin; Kleinpeter, F. Lee; Maccubbin, Elise; Taga, Ken

2005-01-01

This study compared the fears and behavior problems of 25 children with an autism spectrum disorder (ASD), 43 children with Down syndrome (DS), 45 mental age (MA) matched children, and 37 chronologically age (CA) matched children. Children's fears, phobias, anxieties and behavioral problems were assessed using parent reports. Significant…

Inclined Zenith Aurora over Kyoto on 17 September 1770: Graphical Evidence of Extreme Magnetic Storm

NASA Astrophysics Data System (ADS)

Kataoka, Ryuho; Iwahashi, Kiyomi

2017-10-01

Red auroras were observed in Japan during an extreme magnetic storm that occurred on 17 September 1770. We show new evidence that the red aurora extended toward the zenith of Kyoto around midnight. The basic appearance of the historical painting of the red aurora is geometrically reproduced based on the inclination of the local magnetic field and a detailed description in a newly discovered diary. The presence of the inclined zenith aurora over Kyoto suggests that the intensity of the September 1770 magnetic storm is comparable to, or slightly larger than that of the September 1859 Carrington storm.

Associations Between Physical Fitness Indices and Working Memory in Breast Cancer Survivors and Age-Matched Controls

PubMed Central

Mackenzie, Michael J.; Zuniga, Krystle E.; Raine, Lauren B.; Awick, Elizabeth A.; Hillman, Charles H.; Kramer, Arthur F.

2016-01-01

Abstract Background: This study examined the effects of cardiorespiratory fitness, heart rate recovery, and physical activity on working memory in breast cancer survivors and age-matched controls. Method: Using a case-control design, 32 women who had received a breast cancer diagnosis and completed primary treatment within the past 36-months (11 radiation only; 21 chemotherapy) and 30 age-matched women with no previous cancer diagnosis completed a n-back continuous performance task commonly used as an assessment of working memory. In addition, cardiorespiratory fitness and heart rate recovery were measured during a submaximal graded exercise test and physical activity was measured using 7-days of accelerometer monitoring. Results: Breast cancer survivors who had received chemotherapy had poorer heart rate recovery (p = .010) and engaged in less physical activity than women who had received radiation only (p = .004) or non-cancer controls (p = .029). Cancer treatment (radiation; chemotherapy) predicted differences in reaction times on the 1-back working memory task (p = .029). However, more rapid heart rate recovery predicted shorter reaction times on the 1-back task in the age-matched control group (p = .002). All participants with greater cardiorespiratory fitness displayed greater accuracy independent of disease status on the 1-back task (p = .017). No significant group differences in reaction times were observed for 2-back target trials between breast cancer survivors and controls. However, greater total physical activity predicted shorter reaction times in breast cancer survivors (radiation, chemotherapy) on the 2-back task (p = .014). In addition, all participants who exhibited more rapid heart rate recovery demonstrated better greater accuracy regardless of disease status (p = .013). Conclusion: These findings support differences in physical activty participation, heart rate recovery, and 1- and 2-back working memory reaction

The Kyoto Protocol and forestry practices in the United States

Treesearch

Bov B. Eav; Richard A. Birdsey; Linda S. Heath

2000-01-01

Forestry may play an important if not critical role in the ability of the U.S. to meet its greenhouse gas emissions target under the terms of the Kyoto Protocol. Given the low rate of change in the U.S. forest land area, the major anthropogenic influences on the current net forest carbon flux are forest management and protection activities that have resulted in...

Age-Related Brain Activation Changes during Rule Repetition in Word-Matching.

PubMed

Methqal, Ikram; Pinsard, Basile; Amiri, Mahnoush; Wilson, Maximiliano A; Monchi, Oury; Provost, Jean-Sebastien; Joanette, Yves

2017-01-01

Objective: The purpose of this study was to explore the age-related brain activation changes during a word-matching semantic-category-based task, which required either repeating or changing a semantic rule to be applied. In order to do so, a word-semantic rule-based task was adapted from the Wisconsin Sorting Card Test, involving the repeated feedback-driven selection of given pairs of words based on semantic category-based criteria. Method: Forty healthy adults (20 younger and 20 older) performed a word-matching task while undergoing a fMRI scan in which they were required to pair a target word with another word from a group of three words. The required pairing is based on three word-pair semantic rules which correspond to different levels of semantic control demands: functional relatedness, moderately typical-relatedness (which were considered as low control demands), and atypical-relatedness (high control demands). The sorting period consisted of a continuous execution of the same sorting rule and an inferred trial-by-trial feedback was given. Results: Behavioral performance revealed increases in response times and decreases of correct responses according to the level of semantic control demands (functional vs. typical vs. atypical) for both age groups (younger and older) reflecting graded differences in the repetition of the application of a given semantic rule. Neuroimaging findings of significant brain activation showed two main results: (1) Greater task-related activation changes for the repetition of the application of atypical rules relative to typical and functional rules, and (2) Changes (older > younger) in the inferior prefrontal regions for functional rules and more extensive and bilateral activations for typical and atypical rules. Regarding the inter-semantic rules comparison, only task-related activation differences were observed for functional > typical (e.g., inferior parietal and temporal regions bilaterally) and atypical > typical (e

Neuroprotective Effects of MAGL (Monoacylglycerol Lipase) Inhibitors in Experimental Ischemic Stroke.

PubMed

Choi, Sang-Ho; Arai, Allison L; Mou, Yongshan; Kang, Byeongteck; Yen, Cecil Chern-Chyi; Hallenbeck, John; Silva, Afonso C

2018-03-01

MAGL (monoacylglycerol lipase) is an enzyme that hydrolyzes the endocannabinoid 2-arachidonoylglycerol and regulates the production of arachidonic acid and prostaglandins-substances that mediate tissue inflammatory response. Here, we have studied the effects of the selective MAGL inhibitors JZL184 and MJN110 and their underlying molecular mechanisms on 3 different experimental models of focal cerebral ischemia. SHR (spontaneously hypertensive rats) and normotensive WKY (Wistar Kyoto) rats were subject to an intracortical injection of the potent vasoconstrictor endothelin-1, permanent occlusion of a distal segment of the middle cerebral artery via craniectomy, or transient occlusion of the middle cerebral artery by the intraluminal suture method. JZL184 or MJN110 was administered 60 minutes after focal cerebral ischemia. Infarct volumes, hemispheric swelling, and functional outcomes were assessed between days 1 to 28 by magnetic resonance imaging, histology, and behavioral tests. Pharmacological inhibition of MAGL significantly attenuated infarct volume and hemispheric swelling. MAGL inhibition also ameliorated sensorimotor deficits, suppressed inflammatory response, and decreased the number of degenerating neurons. These beneficial effects of MAGL inhibition were not fully abrogated by selective antagonists of cannabinoid receptors, indicating that the anti-inflammatory effects are caused by inhibition of eicosanoid production rather than by activation of cannabinoid receptors. Our results suggest that MAGL may contribute to the pathophysiology of focal cerebral ischemia and is thus a promising therapeutic target for the treatment of ischemic stroke. © 2018 American Heart Association, Inc.

Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat

NASA Technical Reports Server (NTRS)

Wang, T. M.; Hsu, J. F.; Jee, W. S.; Matthews, J. L.

1993-01-01

The histomorphometric changes in the proximal tibial metaphysis and epiphyseal growth plate and midtibial shaft of 26-week-old spontaneously hypertensive rats (SHR) compared with those of the corresponding normotensive Wistar-Kyoto (WKY) rats were studied. A decrease in body weight, growth plate thickness, and longitudinal growth rate of the proximal tibial epiphysis, trabecular bone volume, trabecular thickness and number, the number of osteoblasts and osteoprogenitor cells per millimeter square surface of the proximal tibial metaphysis, periosteal and endocortical apposition rate and bone formation rate of the tibial diaphysis were observed in the SHR. Additionally, systolic blood pressure, the number of osteoclasts per millimeter square surface and average number of nuclei per osteoclast of the proximal tibial metaphysis were significantly increased. Thus, osteoclastic activity is dominant over osteoblastic and chondroblastic activity in the SHR that results in a cancellous bone deficit in the skeleton. It will require additional work to ascertain the underlying cause for this condition as several factors in the SHR with a potential for causing this change are present, including elevated parathyroid hormone (PTH), depressed 1,25-(OH)2D3, low calcium absorption, reduced body weight (reduced loading) elevated blood pressure and possibly other direct cell differences in the mutant strain. At present elevated PTH and adaptation to underloading from reduced weight are postulated to be a likely cause, but additional studies are required to test this interpretation.

Magnetic resonance imaging based morphologic evaluation of the pineal gland for suspected pineoblastoma in retinoblastoma patients and age-matched controls.

PubMed

Pham, Thi Thai Hien; Siebert, Eberhard; Asbach, Patrick; Willerding, Gregor; Erb-Eigner, Katharina

2015-12-15

The purpose of this study was to evaluate the morphologic magnetic resonance imaging (MRI) characteristics of the pineal gland in retinoblastoma (Rb) patients without and with pineoblastoma in comparison to age-matched controls to improve early identification of pineoblastomas (trilateral retinoblastoma, TRb). 80 patients with retinoblastoma and 80 age-matched controls who had undergone brain MRI were included in this retrospective institutional review board approved cohort study. Two readers analyzed the following MR characteristics of the pineal gland: signal intensity on T1- and T2-weighted images, enhancement pattern, delineation of the gland, presence of cystic component, size of pineal gland and size of pineal cysts, respectively. A third reader assessed all images for the presence or absence of pineoblastoma. 3 patients were positive (TRb cohort) and 77 negative for pineoblastoma (non-TRb cohort). The mean maximum diameter of the pineal gland was 6.4mm in Rb patients and 6.3mm in age-matched controls. The mean volume of the pineal gland in Rb patients was 93.1mm(3) and was 87.6mm(3) in age-matched controls. Considering all available MRI scans the mean maximum diameter of the pineal gland in TRb patients was 11.2mm and the mean volume in TRb patients was 453.3mm(3). The third reader identified pineoblastomas with a sensitivity of 100% (3 of 3) and a specificity of 94% (72 of 77). Our non-TRb patients did not show significant differences in the size of the pineal gland and pineal gland cysts compared to age-matched controls. The presented data can serve as a reference for the volume of normal pineal glands and pineal cysts in the diagnostic work-up of Rb patients with suspected pineoblastoma. Copyright © 2015 Elsevier B.V. All rights reserved.

Tracing of Zinc Nanocrystals in the Anterior Pituitary of Zinc-Deficient Wistar Rats.

PubMed

Kuldeep, Anjana; Nair, Neena; Bedwal, Ranveer Singh

2017-06-01

The aim of this study was to trace zinc nanocrystals in the anterior pituitary of zinc-deficient Wistar rats by using autometallographic technique. Male Wistar rats (30-40 days of age, pre-pubertal period) of 40-50 g body weight were divided into the following: the ZC (zinc control) group-fed with 100 ppm zinc in diet, the ZD (zinc-deficient) group-fed with zinc-deficient (1.00 ppm) diet and the PF (pair-fed) group-received 100 ppm zinc in diet. The experiments were set for 2 and 4 weeks. Pituitary was removed and processed for the autometallographic technique. The control and pair-fed groups retained their normal morphological features. However, male Wistar rats fed on zinc-deficient diet for 2 and 4 weeks displayed a wide range of symptoms such as significant (P < 0.05) decrease in diet consumption, body weight and pituitary weight and decrease in gradation of intensity of zinc nanocrystals in the nuclei. The present findings suggest that the dietary zinc deficiency causes decreased intensity of zinc nanocrystals localization and their distribution in the pituitary thereby contributing to the dysfunction of the pituitary of the male Wistar rats. The severity of zinc deficiency symptoms progressed after the second week of the experiment. Decreased intensity of zinc nanocrystals attenuates the pituitary function which would exert its affect on other endocrine organs impairing their functions indicating that the metabolic regulation of pituitary is mediated to a certain extent by zinc and/or hypothalamus-hypophysial system which also reflects its essentiality during the period of growth.

[Climate change and Kyoto protocol].

PubMed

Ergasti, G; Pippia, V; Murzilli, G; De Luca D'Alessandro, E

2009-01-01

Due to industrial revolution and the heavy use of fossil fuels, the concentration of greenhouse gases in the atmosphere has increased dramatically during the last hundred years, and this has lead to an increase in mean global temperature. The environmental consequences of this are: the melting of the ice caps, an increase in mean sea-levels, catastrophic events such as floodings, hurricanes and earthquakes, changes to the animal and vegetable kingdoms, a growth in vectors and bacteria in water thus increasing the risk of infectious diseases and damage to agriculture. The toxic effects of the pollution on human health are both acute and chronic. The Kyoto Protocol is an important step in the campaign against climatic changes but it is not sufficient. A possible solution might be for the States which produce the most of pollution to adopt a better political stance for the environment and to use renewable resources for the production of energy.

Recall Memory in Children with Down Syndrome and Typically Developing Peers Matched on Developmental Age

ERIC Educational Resources Information Center

Milojevich, H.; Lukowski, A.

2016-01-01

Background: Whereas research has indicated that children with Down syndrome (DS) imitate demonstrated actions over short delays, it is presently unknown whether children with DS recall information over lengthy delays at levels comparable with typically developing (TD) children matched on developmental age. Method: In the present research, 10…

Allanite age-dating: Non-matrix-matched standardization in quadrupole LA-ICP-MS

NASA Astrophysics Data System (ADS)

Burn, M.; Lanari, P.; Pettke, T.; Engi, M.

2014-12-01

Allanite Th-U-Pb age-dating has recently been found to be powerful in unraveling the timing of geological processes such as the metamorphic dynamics in subduction zones and crystallization velocity of magmas. However, inconsistencies among analytical techniques have raised doubts about the accuracy of allanite age data. Spot analysis techniques such as LA-ICP-MS are claimed to be crucially dependent on matrix-matched standards, the quality of which is variable. We present a new approach in LA-ICP-MS data reduction that allows non-matrix-matched standardization via well constrained zircon reference materials as primary standards. Our data were obtained using a GeoLas Pro 193 nm ArF excimer laser ablation system coupled to an ELAN DRC-e quadrupole ICP-MS. We use 32 μm and 24 μm spot sizes; laser operating conditions of 9 Hz repetition rate and 2.5 J/cm2 fluence have proven advantageous. Matrix dependent downhole fractionation evolution is empirically determined by analyzing 208Pb/232Th and 206Pb/238U and applied prior to standardization. The new data reduction technique was tested on three magmatic allanite reference materials (SISSb, CAPb, TARA); within error these show the same downhole fractionation evolution for all allanite types and in different analytical sessions, provided measurement conditions remain the same. Although the downhole evolution of allanite and zircon differs significantly, a link between zircon and allanite matrix is established by assuming CAPb and TARA to be fixed at the corresponding reference ages. Our weighted mean 208Pb/232Th ages are 30.06 ± 0.22 (2σ) for SISSb, 275.4 ± 1.3 (2σ) for CAPb, and 409.9 ± 1.8 (2σ) for TARA. Precision of single spot age data varies between 1.5 and 8 % (2σ), dependent on spot size and common lead concentrations. Quadrupole LA-ICP-MS allanite age-dating has thus similar uncertainties as do other spot analysis techniques. The new data reduction technique is much less dependent on quality and homogeneity

Dosimetry considerations in the enhanced sensitivity of male Wistar rats to chronic ethylene glycol-induced nephrotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Corley, R.A.; Wilson, D.M.; Hard, G.C.

2008-04-15

rats (a less sensitive strain), a significant difference was observed in oxalate clearances between young rats (i.e. Wistar clearance < F344) but not in age-matched old rats. Regardless, the ratios of oxalate:inulin clearances in these two strains of rats, including those exposed to ethylene glycol, were all < 1, suggesting that a fraction of the filtered oxalate is reabsorbed. Other species, including humans, typically have clearance ratios > 1 and are more effective at clearing oxalic acid by both glomerular filtration and active secretion. Thus, the lower renal clearance and kidney accumulation of oxalates in male Wistar rats enhances their sensitivity, which will be a factor in human risk assessments. The benchmark dose values (BMD05, BMDL05) were 170 mg/kg/day and 150 mg/kg/day for nephropathy, and 170 mg/kg/day and 160 mg/kg/day for birefringent crystals, using incidence times severity data in each case. The NOAEL of 150 mg/kg/day is the same as that reported after 16-week exposure and appears to be a threshold dose below which no renal toxicity occurs, regardless of exposure duration.« less

Kyoto global consensus report on Helicobacter pylori gastritis

PubMed Central

Sugano, Kentaro; Tack, Jan; Kuipers, Ernst J; Graham, David Y; El-Omar, Emad M; Miura, Soichiro; Haruma, Ken; Asaka, Masahiro; Uemura, Naomi; Malfertheiner, Peter

2015-01-01

Objective To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat H. pylori gastritis. Design Twenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels were asked to formulate relevant statements. A Delphi method using an anonymous electronic system was adopted to develop the consensus, the level of which was predefined as ≥80%. Final modifications of clinical questions and consensus were achieved at the face-to-face meeting in Kyoto. Results All 24 statements for 22 clinical questions after extensive modifications and omission of one clinical question were achieved with a consensus level of >80%. To better organise classification of gastritis and duodenitis based on aetiology, a new classification of gastritis and duodenitis is recommended for the 11th international classification. A new category of H. pylori-associated dyspepsia together with a diagnostic algorithm was proposed. The adoption of grading systems for gastric cancer risk stratification, and modern image-enhancing endoscopy for the diagnosis of gastritis, were recommended. Treatment to eradicate H. pylori infection before preneoplastic changes develop, if feasible, was recommended to minimise the risk of more serious complications of the infection. Conclusions A global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject. PMID:26187502

Decreased catecholamine secretion from the adrenal medullae of chronically diabetic BB-Wistar rats

NASA Technical Reports Server (NTRS)

Wilke, R. A.; Riley, D. A.; Lelkes, P. I.; Hillard, C. J.

1993-01-01

Many humans with IDDM eventually lose the capacity to secrete epinephrine from their adrenal medullae. The mechanism for this pathological change is unknown. We hypothesized that this abnormality is attributable to neuropathic changes in the greater splanchnic nerves or in the chromaffin cells that they innervate. To study this hypothesis, we isolated rat adrenal glands, perfused them ex vivo, and measured the epinephrine content of the perfusate under various conditions of stimulation. We used transmural electrical stimulation (20-80 V, at 10 Hz) to induce epinephrine secretion indirectly by selectively activating residual splanchnic nerve terminals within the isolated glands. Under these conditions, epinephrine secretion was severely attenuated in glands from female BB-Wistar rats with diabetes of 4 mo duration compared with their age-matched, nondiabetic controls. These perfused diabetic adrenal medullae also demonstrated decreased catecholamine release in response to direct chromaffin cell depolarization with 20 mM K+, evidence that a functional alteration exists within the chromaffin cells themselves. Nonetheless, total catecholamine content of adrenal medullae from these diabetic rats was not significantly different from controls, indicating that the secretory defect was not simply attributable to a difference in the amount of catecholamines stored and available for release. Herein, we also provide histological evidence of degenerative changes within the cholinergic nerve terminals that innervate these glands.

Attention problems of very preterm children compared with age-matched term controls at school-age.

PubMed

de Kieviet, Jorrit F; van Elburg, Ruurd M; Lafeber, Harrie N; Oosterlaan, Jaap

2012-11-01

To clarify the severity, specificity, and neurocognitive underpinnings of attention problems in very preterm children. A sample of 66 preterm (<32 weeks gestation), mean (SD) age 7.5 (0.4) years, and 66 age-matched term controls participated. Symptoms of inattention were assessed using parent and teacher-rated questionnaires, and neurocognitive measures included speed and consistency in speed of information processing, lapses of attention (tau), alerting, orienting, and executive attention, as well as verbal and visuospatial working memory. Group differences were investigated using ANOVA, and Sobel tests were used to clarify the mediating role of neurocognitive impairments on attention problems. There was a large decrease in visuospatial working memory abilities (P < .001, d = .87), and medium increases in tau (P = .002, d = 0.55) as well as parent and teacher ratings of inattention (range d = 0.40-0.56) in very preterm children compared with term peers. Tau and visuospatial working memory were significant predictors of parent (R(2) = .161, P < .001 and R(2) = .071, P = .001; respectively) and teacher (R(2) = .152, P < .001 and R(2) = .064, P = .002; respectively) ratings of inattention, and completely explained the effects of very preterm birth on attention problems. Increased lapses of attention and poorer visuospatial working memory fully account for the attention problems in very premature children at school-age. Copyright © 2012 Mosby, Inc. All rights reserved.

Unconditional or Conditional Logistic Regression Model for Age-Matched Case-Control Data?

PubMed

Kuo, Chia-Ling; Duan, Yinghui; Grady, James

2018-01-01

Matching on demographic variables is commonly used in case-control studies to adjust for confounding at the design stage. There is a presumption that matched data need to be analyzed by matched methods. Conditional logistic regression has become a standard for matched case-control data to tackle the sparse data problem. The sparse data problem, however, may not be a concern for loose-matching data when the matching between cases and controls is not unique, and one case can be matched to other controls without substantially changing the association. Data matched on a few demographic variables are clearly loose-matching data, and we hypothesize that unconditional logistic regression is a proper method to perform. To address the hypothesis, we compare unconditional and conditional logistic regression models by precision in estimates and hypothesis testing using simulated matched case-control data. Our results support our hypothesis; however, the unconditional model is not as robust as the conditional model to the matching distortion that the matching process not only makes cases and controls similar for matching variables but also for the exposure status. When the study design involves other complex features or the computational burden is high, matching in loose-matching data can be ignored for negligible loss in testing and estimation if the distributions of matching variables are not extremely different between cases and controls.

Unconditional or Conditional Logistic Regression Model for Age-Matched Case–Control Data?

PubMed Central

Kuo, Chia-Ling; Duan, Yinghui; Grady, James

2018-01-01

Matching on demographic variables is commonly used in case–control studies to adjust for confounding at the design stage. There is a presumption that matched data need to be analyzed by matched methods. Conditional logistic regression has become a standard for matched case–control data to tackle the sparse data problem. The sparse data problem, however, may not be a concern for loose-matching data when the matching between cases and controls is not unique, and one case can be matched to other controls without substantially changing the association. Data matched on a few demographic variables are clearly loose-matching data, and we hypothesize that unconditional logistic regression is a proper method to perform. To address the hypothesis, we compare unconditional and conditional logistic regression models by precision in estimates and hypothesis testing using simulated matched case–control data. Our results support our hypothesis; however, the unconditional model is not as robust as the conditional model to the matching distortion that the matching process not only makes cases and controls similar for matching variables but also for the exposure status. When the study design involves other complex features or the computational burden is high, matching in loose-matching data can be ignored for negligible loss in testing and estimation if the distributions of matching variables are not extremely different between cases and controls. PMID:29552553

Efficacy of the Kyoto Classification of Gastritis in Identifying Patients at High Risk for Gastric Cancer.

PubMed

Sugimoto, Mitsushige; Ban, Hiromitsu; Ichikawa, Hitomi; Sahara, Shu; Otsuka, Taketo; Inatomi, Osamu; Bamba, Shigeki; Furuta, Takahisa; Andoh, Akira

2017-01-01

Objective The Kyoto gastritis classification categorizes the endoscopic characteristics of Helicobacter pylori (H. pylori) infection-associated gastritis and identifies patterns associated with a high risk of gastric cancer. We investigated its efficacy, comparing scores in patients with H. pylori-associated gastritis and with gastric cancer. Methods A total of 1,200 patients with H. pylori-positive gastritis alone (n=932), early-stage H. pylori-positive gastric cancer (n=189), and successfully treated H. pylori-negative cancer (n=79) were endoscopically graded according to the Kyoto gastritis classification for atrophy, intestinal metaplasia, fold hypertrophy, nodularity, and diffuse redness. Results The prevalence of O-II/O-III-type atrophy according to the Kimura-Takemoto classification in early-stage H. pylori-positive gastric cancer and successfully treated H. pylori-negative cancer groups was 45.1%, which was significantly higher than in subjects with gastritis alone (12.7%, p<0.001). Kyoto gastritis scores of atrophy and intestinal metaplasia in the H. pylori-positive cancer group were significantly higher than in subjects with gastritis alone (all p<0.001). No significant differences were noted in the rates of gastric fold hypertrophy or diffuse redness between the two groups. In a multivariate analysis, the risks for H. pylori-positive gastric cancer increased with intestinal metaplasia (odds ratio: 4.453, 95% confidence interval: 3.332-5.950, <0.001) and male sex (1.737, 1.102-2.739, p=0.017). Conclusion Making an appropriate diagnosis and detecting patients at high risk is crucial for achieving total eradication of gastric cancer. The scores of intestinal metaplasia and atrophy of the scoring system in the Kyoto gastritis classification may thus be useful for detecting these patients.

Differences in monthly variation, cause, and place of injury between femoral neck and trochanteric fractures: 6-year survey (2008–2013) in Kyoto prefecture, Japan

PubMed Central

Horii, Motoyuki; Fujiwara, Hiroyoshi; Mikami, Yasuo; Ikeda, Takumi; Ueshima, Keiichiro; Ikoma, Kazuya; Shirai, Toshiharu; Nagae, Masateru; Oka, Yoshinobu; Sawada, Koshiro; Kuriyama, Nagato; Kubo, Toshikazu

2016-01-01

Summary Background The incidence of femoral neck and trochanteric fractures reportedly differ by age and regionality. We investigated differences in monthly variations of the occurrence of femoral neck and trochanteric fractures as well as place and cause of injury in the Kyoto prefecture over a 6-year period. Methods Fracture type (neck or trochanteric fracture), age, sex, place of injury, and cause of injury were surveyed among patients aged ≥ 65 years with hip fractures that occurred between 2008 and 2013 who were treated in 1 of 13 participating hospitals (5 in an urban area and 8 in a rural area). The proportion of sick beds in the participating hospitals was 24.7% (4,151/16,781). Monthly variations in the number of patients were investigated in urban and rural areas in addition to the entire Kyoto prefecture. Place of injury was classified as indoors or outdoors, and cause of injury was categorized as simple fall, accident, or uncertain. Results There were 2,826 patients with neck fractures (mean age, 82.1 years) and 3,305 patients with trochanteric fractures (mean age, 85.0 years). There were similarities in the monthly variation of the number of fractures in addition to the place and cause of injury between neck and trochanteric fractures. Indoors (approximately 74%) and simple falls (approximately 78%) were the primary place and cause of injury, respectively. The place of injury was not significantly different by fracture type with each age group. Significantly more patients with neck fracture had “uncertain” as the cause of injury than trochanteric fracture in all age groups. Conclusions Based on the results of the present study, the injury pattern might not have a great effect on the susceptibility difference between neck and trochanteric fractures. PMID:27252738

Postural adjustments in young ballet dancers compared to age matched controls.

PubMed

Iunes, Denise H; Elias, Iara F; Carvalho, Leonardo C; Dionísio, Valdeci C

2016-01-01

The purpose of the study was to use photogrammetry to evaluate the posture of ballet practitioners compared to an age-matched control group. One hundred and eleven 7- to 24-year-old female volunteers were evaluated and were divided into two groups: the ballet practising group (n = 52) and the control group (n = 59), divided into three subgroups according to age and years of ballet experience. Dancers with 1-3 years experience compared to controls of the same age shows alterations in External Rotation Angle (P < 0.05). Dancers 4-9 years experience show alterations in Lumbar Lordosis, Pelvis Tilt Angle and Navicular Angle Right and Left (P < 0.05). Dancers with over 9 years experience show alterations in External Rotation and Navicular Angle Left (P < 0.05). Research shows there are differences between dancers and controls. In the groups 1-3 years and over 9 years of experience, the External Rotation Angle is greater. In the group 4-9 years of experience the Lumbar Lordosis Angle is greater and Pelvis Tilt, Navicular Angle Left and Right are smaller. In more than 9 years of ballet experience, the Navicular Angle Left is smaller. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nature and nurture: environmental influences on a genetic rat model of depression.

PubMed

Mehta-Raghavan, N S; Wert, S L; Morley, C; Graf, E N; Redei, E E

2016-03-29

In this study, we sought to learn whether adverse events such as chronic restraint stress (CRS), or 'nurture' in the form of environmental enrichment (EE), could modify depression-like behavior and blood biomarker transcript levels in a genetic rat model of depression. The Wistar Kyoto More Immobile (WMI) is a genetic model of depression that aided in the identification of blood transcriptomic markers, which successfully distinguished adolescent and adult subjects with major depressive disorders from their matched no-disorder controls. Here, we followed the effects of CRS and EE in adult male WMIs and their genetically similar control strain, the Wistar Kyoto Less Immobile (WLI), that does not show depression-like behavior, by measuring the levels of these transcripts in the blood and hippocampus. In WLIs, increased depression-like behavior and transcriptomic changes were present in response to CRS, but in WMIs no behavioral or additive transcriptomic changes occurred. Environmental enrichment decreased both the inherent depression-like behavior in the WMIs and the behavioral difference between WMIs and WLIs, but did not reverse basal transcript level differences between the strains. The inverse behavioral change induced by CRS and EE in the WLIs did not result in parallel inverse expression changes of the transcriptomic markers, suggesting that these behavioral responses to the environment work via separate molecular pathways. In contrast, 'trait' transcriptomic markers with expression differences inherent and unchanging between the strains regardless of the environment suggest that in our model, environmental and genetic etiologies of depression work through independent molecular mechanisms.

Nature and nurture: environmental influences on a genetic rat model of depression

PubMed Central

Mehta-Raghavan, N S; Wert, S L; Morley, C; Graf, E N; Redei, E E

2016-01-01

In this study, we sought to learn whether adverse events such as chronic restraint stress (CRS), or ‘nurture' in the form of environmental enrichment (EE), could modify depression-like behavior and blood biomarker transcript levels in a genetic rat model of depression. The Wistar Kyoto More Immobile (WMI) is a genetic model of depression that aided in the identification of blood transcriptomic markers, which successfully distinguished adolescent and adult subjects with major depressive disorders from their matched no-disorder controls. Here, we followed the effects of CRS and EE in adult male WMIs and their genetically similar control strain, the Wistar Kyoto Less Immobile (WLI), that does not show depression-like behavior, by measuring the levels of these transcripts in the blood and hippocampus. In WLIs, increased depression-like behavior and transcriptomic changes were present in response to CRS, but in WMIs no behavioral or additive transcriptomic changes occurred. Environmental enrichment decreased both the inherent depression-like behavior in the WMIs and the behavioral difference between WMIs and WLIs, but did not reverse basal transcript level differences between the strains. The inverse behavioral change induced by CRS and EE in the WLIs did not result in parallel inverse expression changes of the transcriptomic markers, suggesting that these behavioral responses to the environment work via separate molecular pathways. In contrast, ‘trait' transcriptomic markers with expression differences inherent and unchanging between the strains regardless of the environment suggest that in our model, environmental and genetic etiologies of depression work through independent molecular mechanisms. PMID:27023176

Long-term administration of Greek Royal Jelly decreases GABA concentration in the striatum and hypothalamus of naturally aged Wistar male rats.

PubMed

Pyrzanowska, Justyna; Wawer, Adriana; Joniec-Maciejak, Ilona; Piechal, Agnieszka; Blecharz-Klin, Kamilla; Graikou, Konstantia; Chinou, Ioanna; Widy-Tyszkiewicz, Ewa

2018-05-14

Royal Jelly (RJ) is a unique substance obtained from bees that has been used widely in European and Asian traditional medicine for its potential to prevent signs of aging through its antioxidative, anti-inflammatory, anti-hyperglycemic and anti-hypercholesterolemic properties. We recently reported an enhancement in spatial memory along with changes in monoaminergic transmission in aged rats after chronic RJ administration. Here, we aim to further explore the action of RJ on central nervous system activity by examining levels of amino acids in selected brain structures of aged male Wistar rats following 2-months of Greek RJ administration. RJ powder was previously chemically characterized and given orally (50 or 100 mg of powder/kg b.w./day) by gastric gavage. The concentrations of amino acids (alanine, aspartic acid, gamma-aminobutyric acid, glutamic acid, histidine and taurine) in the brain regions examined (prefrontal cortex, hippocampus, striatum and hypothalamus) were quantified using HPLC. We also examined basic biochemical parameters of renal and hepatic activity, as damage of these organs could potentially explain the changes in brain function and behavior. Upon biochemical examination, a decrease in the concentration of gamma-aminobutyric acid was observed in both the striatum and hypothalamus. Liver and kidney functions were not changed by chronic RJ-administration. Our results provide insight toward understanding the mechanism of action of RJ and its effects on neurotransmission in the central nervous system. Copyright © 2018 Elsevier B.V. All rights reserved.

NPY1–36 and PYY1–36 activate cardiac fibroblasts: an effect enhanced by genetic hypertension and inhibition of dipeptidyl peptidase 4

PubMed Central

Zhu, Xiao; Gillespie, Delbert G.

2015-01-01

Cardiac sympathetic nerves release neuropeptide Y (NPY)1–36, and peptide YY (PYY)1–36 is a circulating peptide; therefore, these PP-fold peptides could affect cardiac fibroblasts (CFs). We examined the effects of NPY1–36 and PYY1–36 on the proliferation of and collagen production ([3H]proline incorporation) by CFs isolated from Wistar-Kyoto (WKY) normotensive rats and spontaneously hypertensive rats (SHRs). Experiments were performed with and without sitagliptin, an inhibitor of dipeptidyl peptidase 4 [DPP4; an ectoenzyme that metabolizes NPY1–36 and PYY1–36 (Y1 receptor agonists) to NPY3–36 and PYY3–36 (inactive at Y1 receptors), respectively]. NPY1–36 and PYY1–36, but not NPY3–36 or PYY3–36, stimulated proliferation of CFs, and these effects were more potent than ANG II, enhanced by sitagliptin, blocked by BIBP3226 (Y1 receptor antagonist), and greater in SHR CFs. SHR CF membranes expressed more receptor for activated C kinase (RACK)1 [which scaffolds the Gi/phospholipase C (PLC)/PKC pathway] compared with WKY CF membranes. RACK1 knockdown (short hairpin RNA) and inhibition of Gi (pertussis toxin), PLC (U73122), and PKC (GF109203X) blocked the proliferative effects of NPY1–36. NPY1–36 and PYY1–36 stimulated collagen production more potently than did ANG II, and this was enhanced by sitagliptin and greater in SHR CFs. In conclusion, 1) NPY1–36 and PYY1–36, via the Y1 receptor/Gi/PLC/PKC pathway, activate CFs, and this pathway is enhanced in SHR CFs due to increased localization of RACK1 in membranes; and 2) DPP4 inhibition enhances the effects of NPY1–36 and PYY1–36 on CFs, likely by inhibiting the metabolism of NPY1–36 and PYY1–36. The implications are that endogenous NPY1–36 and PYY1–36 could adversely affect cardiac structure/function by activating CFs, and this may be exacerbated in genetic hypertension and by DPP4 inhibitors. PMID:26371160

Autophagy is altered in skeletal and cardiac muscle of spontaneously hypertensive rats.

PubMed

Bloemberg, D; McDonald, E; Dulay, D; Quadrilatero, J

2014-02-01

Autophagy is a subcellular degradation mechanism important for muscle maintenance. Hypertension induces well-characterized pathological changes to the heart and is associated with impaired function and increased apoptotic signalling in skeletal muscle. We examined whether essential hypertension affects several autophagy markers in skeletal and cardiac muscle. Immunoblotting and qRT-PCR were used to measure autophagy-related proteins/mRNA in multiple skeletal muscles as well as left ventricle (LV) of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Skeletal muscles of hypertensive rats had decreased (P < 0.01) cross-sectional area of type I fibres (e.g. soleus WKY: 2952.9 ± 64.4 μm(2) vs. SHR: 2579.9 ± 85.8 μm(2)) and a fibre redistribution towards a 'fast' phenotype. Immunoblot analysis revealed that some SHR skeletal muscles displayed a decreased LC3II/I ratio (P < 0.05), but none showed differences in p62 protein. LC3 and LAMP2 mRNA levels were increased approx. 2-3-fold in all skeletal muscles (P < 0.05), while cathepsin activity, cathepsin L mRNA and Atg7 protein were increased 16-17% (P < 0.01), 2-3-fold (P < 0.05) and 29-49% (P < 0.01), respectively, in fast muscles of hypertensive animals. Finally, protein levels of BAG3, a marker of chaperone-assisted selective autophagy, were 18-25% lower (P < 0.05) in SHR skeletal muscles. In the LV of SHR, LC3I and p62 protein were elevated 34% (P < 0.05) and 47% (P < 0.01), respectively. Furthermore, p62 mRNA was 68% higher (P < 0.05), while LAMP2 mRNA was 45% lower (P < 0.05), in SHR cardiac muscle. There was no difference in Beclin1, Atg7, Bnip3 or BAG3 protein in the LV between strains. These results suggest that autophagy is altered in skeletal and cardiac muscle during hypertension. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

TLR4/MyD88/NF-κB signaling and PPAR-γ within the paraventricular nucleus are involved in the effects of telmisartan in hypertension

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Hong-Bao; Li, Xiang; Huo, Chan-Juan

Previous findings from our laboratory and others indicate that the main therapeutic effect of angiotensin II type 1 receptor (AT1-R) antagonists is to decrease blood pressure and exert anti-inflammatory effects in the cardiovascular system. In this study, we determined whether AT1-R antagonist telmisartan within the hypothalamic paraventricular nucleus (PVN) attenuates hypertension and hypothalamic inflammation via both the TLR4/MyD88/NF-κB signaling pathway and peroxisome proliferator-activated receptor-γ (PPAR-γ) in the PVN in hypertensive rats. Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats were treated for 4 weeks through bilateral PVN infusion with the AT1-R antagonist telmisartan (TEL, 10 μg/h), or losartanmore » (LOS, 20 μg/h), or the PPAR-γ antagonist GW9662 (GW, 100 μg/h), or vehicle via osmotic minipump. Mean arterial pressure (MAP) was recorded by a tail-cuff occlusion method. PVN tissue and blood were collected for the measurement of AT1-R, PPAR-γ, pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6), inducible nitric oxide synthase (iNOS), TLR4, MyD88, nuclear factor-kappa B (NF-κB) activity and plasma norepinephrine (NE), respectively. Hypertensive rats exhibited significantly higher level of AT1-R and lower level of PPAR-γ in the PVN. PVN treatment with TEL attenuated MAP, improved cardiac hypertrophy, reduced TNF-α, IL-1β, IL-6, iNOS levels, and plasma NE in SHR but not in WKY rats. These results were associated with reduced TLR4, MyD88 and NF-κB levels and increased PPAR-γ level in the PVN of hypertensive rats. Our findings suggest that TLR4/MyD88/NF-κB signaling and PPAR-γ within the PVN are involved in the beneficial effects of telmisartan in hypertension. - Highlights: • PVN infusion of TEL in spontaneously hypertensive rats is reported. • PVN infusion of TEL attenuates hypertension and proinflammatory cytokines in PVN. • PVN blockade of AT1-R attenuates

Inflammatory Role of Macrophage Xanthine Oxidoreductase in Pulmonary Hypertension: Implications for Novel Therapeutic Approaches

DTIC Science & Technology

2015-10-01

Lung Inflammation, Uric Acid, Chronic Obstructive Pulmonary Disease, Mononuclear Phagocyte , Monosodium Urate, XOR WT, XOR KO, Wistar Kyoto, Pulmonary...0451 Annual Report (Year 1) 4 Mononuclear Phagocyte XOR Activity and Superoxide Generation Were Reduced by

Efficacy of the Kyoto Classification of Gastritis in Identifying Patients at High Risk for Gastric Cancer

PubMed Central

Sugimoto, Mitsushige; Ban, Hiromitsu; Ichikawa, Hitomi; Sahara, Shu; Otsuka, Taketo; Inatomi, Osamu; Bamba, Shigeki; Furuta, Takahisa; Andoh, Akira

2017-01-01

Objective The Kyoto gastritis classification categorizes the endoscopic characteristics of Helicobacter pylori (H. pylori) infection-associated gastritis and identifies patterns associated with a high risk of gastric cancer. We investigated its efficacy, comparing scores in patients with H. pylori-associated gastritis and with gastric cancer. Methods A total of 1,200 patients with H. pylori-positive gastritis alone (n=932), early-stage H. pylori-positive gastric cancer (n=189), and successfully treated H. pylori-negative cancer (n=79) were endoscopically graded according to the Kyoto gastritis classification for atrophy, intestinal metaplasia, fold hypertrophy, nodularity, and diffuse redness. Results The prevalence of O-II/O-III-type atrophy according to the Kimura-Takemoto classification in early-stage H. pylori-positive gastric cancer and successfully treated H. pylori-negative cancer groups was 45.1%, which was significantly higher than in subjects with gastritis alone (12.7%, p<0.001). Kyoto gastritis scores of atrophy and intestinal metaplasia in the H. pylori-positive cancer group were significantly higher than in subjects with gastritis alone (all p<0.001). No significant differences were noted in the rates of gastric fold hypertrophy or diffuse redness between the two groups. In a multivariate analysis, the risks for H. pylori-positive gastric cancer increased with intestinal metaplasia (odds ratio: 4.453, 95% confidence interval: 3.332-5.950, <0.001) and male sex (1.737, 1.102-2.739, p=0.017). Conclusion Making an appropriate diagnosis and detecting patients at high risk is crucial for achieving total eradication of gastric cancer. The scores of intestinal metaplasia and atrophy of the scoring system in the Kyoto gastritis classification may thus be useful for detecting these patients. PMID:28321054

Heidelberg-Kyoto partnership bridges life and materials sciences, strengthens bilateral ties.

PubMed

Iijima, Yutaka; Kornhauser, David H; Nakatsuji, Norio

2012-06-01

Coinciding with the 150(th) anniversary of German-Japanese friendship, Kyoto University and Heidelberg University, two universities replete with history and tradition strengthened their close ties at a joint meeting in Heidelberg, Germany, forming the core of a broad collaborative effort between the two countries. This forum article provides a background and overview of the collaborations. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel Mechanism for Disrupted Circadian Blood Pressure Rhythm in a Rat Model of Metabolic Syndrome—The Critical Role of Angiotensin II

PubMed Central

Sueta, Daisuke; Kataoka, Keiichiro; Koibuchi, Nobutaka; Toyama, Kensuke; Uekawa, Ken; Katayama, Tetsuji; MingJie, Ma; Nakagawa, Takashi; Waki, Hidefumi; Maeda, Masanobu; Yasuda, Osamu; Matsui, Kunihiko; Ogawa, Hisao; Kim‐Mitsuyama, Shokei

2013-01-01

Background This study was performed to determine the characteristics and mechanism of hypertension in SHR/NDmcr‐cp(+/+) rats (SHRcp), a new model of metabolic syndrome, with a focus on the autonomic nervous system, aldosterone, and angiotensin II. Methods and Results We measured arterial blood pressure (BP) in SHRcp by radiotelemetry combined with spectral analysis using a fast Fourier transformation algorithm and examined the effect of azilsartan, an AT1 receptor blocker. Compared with control Wistar‐Kyoto rats (WKY) and SHR, SHRcp exhibited a nondipper‐type hypertension and displayed increased urinary norepinephrine excretion and increased urinary and plasma aldosterone levels. Compared with WKY and SHR, SHRcp were characterized by an increase in the low‐frequency power (LF) of systolic BP and a decrease in spontaneous baroreflex gain (sBRG), indicating autonomic dysfunction. Thus, SHRcp are regarded as a useful model of human hypertension with metabolic syndrome. Oral administration of azilsartan once daily persistently lowered BP during the light period (inactive phase) and the dark period (active phase) in SHRcp more than in WKY and SHR. Thus, angiotensin II seems to be involved in the mechanism of disrupted diurnal BP rhythm in SHRcp. Azilsartan significantly reduced urinary norepinephrine and aldosterone excretion and significantly increased urinary sodium excretion in SHRcp. Furthermore, azilsartan significantly reduced LF of systolic BP and significantly increased sBRG in SHRcp. Conclusions These results strongly suggest that impairment of autonomic function and increased aldosterone in SHRcp mediate the effect of angiotensin II on circadian blood pressure rhythms. PMID:23629805

The fears, phobias and anxieties of children with autism spectrum disorders and Down syndrome: comparisons with developmentally and chronologically age matched children.

PubMed

Evans, David W; Canavera, Kristin; Kleinpeter, F Lee; Maccubbin, Elise; Taga, Ken

2005-01-01

This study compared the fears and behavior problems of 25 children with an autism spectrum disorder (ASD), 43 children with Down syndrome (DS), 45 mental age (MA) matched children, and 37 chronologically age (CA) matched children. Children's fears, phobias, anxieties and behavioral problems were assessed using parent reports. Significant differences emerged across the diagnostic groups on a variety of fears. Children with ASD were reported to have more situation phobias and medical fears, but fewer fears of harm/injury compared to all other groups. The groups also differed in terms of the pattern of correlations between fears, phobias, anxieties and behavior problems. For children with ASD, fears, phobias and anxieties were closely related to problem behaviors, whereas fears, phobias, and anxieties were less related to behavioral symptoms for the other groups of subjects. Such findings suggest that children with ASD exhibit a distinct profile of fear and anxiety compared to other mental age and chronologically age-matched children, and these fears are related to the symptoms associated with ASD.

Verification of the ages of supercentenarians in the United States: results of a matching study.

PubMed

Rosenwaike, Ira; Stone, Leslie F

2003-11-01

Unprecedented declines in mortality among the very old have led to the emergence of "true" supercentenarians (persons aged 110 and over). The ages of these individuals have been well-documented in European countries with a history of birth registration, but have not been systematically studied in the United States, which lacks similar documentation and where the inaccuracy of age reporting has been an issue. To verify age, we linked records from the Social Security Administration for close to 700 individuals who died from 1980 to 1999 purportedly at ages 110 and older to records of the U.S. censuses of 1880 and 1900, conducted when these individuals were children. This group was a residual group from an earlier file that was reduced by the SSA after data checks that eliminated incorrect records. The results of the matched records for the residual file indicate that over 90% of the whites were accurately reported as supercentenarians, but only half of the blacks appeared to have attained age 110. The verification of age shows that the United States has more "true" supercentenarians than do other nations.

Kyoto global consensus report on Helicobacter pylori gastritis.

PubMed

Sugano, Kentaro; Tack, Jan; Kuipers, Ernst J; Graham, David Y; El-Omar, Emad M; Miura, Soichiro; Haruma, Ken; Asaka, Masahiro; Uemura, Naomi; Malfertheiner, Peter

2015-09-01

To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat H. pylori gastritis. Twenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels were asked to formulate relevant statements. A Delphi method using an anonymous electronic system was adopted to develop the consensus, the level of which was predefined as ≥80%. Final modifications of clinical questions and consensus were achieved at the face-to-face meeting in Kyoto. All 24 statements for 22 clinical questions after extensive modifications and omission of one clinical question were achieved with a consensus level of >80%. To better organise classification of gastritis and duodenitis based on aetiology, a new classification of gastritis and duodenitis is recommended for the 11th international classification. A new category of H. pylori-associated dyspepsia together with a diagnostic algorithm was proposed. The adoption of grading systems for gastric cancer risk stratification, and modern image-enhancing endoscopy for the diagnosis of gastritis, were recommended. Treatment to eradicate H. pylori infection before preneoplastic changes develop, if feasible, was recommended to minimise the risk of more serious complications of the infection. A global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Daily chronomics of proteomic profile in aging and rotenone-induced Parkinson's disease model in male Wistar rat and its modulation by melatonin.

PubMed

Jagota, Anita; Mattam, Ushodaya

2017-08-01

Aging is associated with changes in several basic parameters of circadian timing system (CTS) in mammals leading to circadian dysfunction. We had reported earlier that upon aging and in rotenone induced Parkinson's disease (RIPD) rat model there were significant alterations in the core clock genes expression levels and daily pulses. To identify biomarkers of aging and PD chronomics of proteomic day-night profiles in suprachiasmatic nucleus (SCN), pineal and substantia nigra (SN) in 3 month (m), 12, 24 m and RIPD rat model were studied at two time points i.e. Zeitgeber Time (ZT)-6 (mid-day) and ZT-18 (mid-night). Proteome analysis was done by using two dimensional (2-D) electrophoresis and the spots showing robust day-night variations were identified by using MALDI TOF/TOF analysis. In 3 m rats the number of proteins showing day-night variations were relatively more than 12, 24 m and RIPD rat model in SCN and SN. But in pineal there was increase in number of protein spots showing day-night variations in 24 m. Mass spectroscopy of the protein spots showing robust day night variation in aging and RIPD rats were identified. As melatonin, a multitasking molecule, an endogenous synchronizer of rhythm, an antioxidant and an antiaging drug, declines with aging, the effects of melatonin administration on differential alterations in chronomics of 2-D protein profiles in aging and RIPD male Wistar rats were studied. We report here that the melatonin could be playing an important role in modulating the chronomics of 2-D protein profiles. Additionally, various proteins were identified for the first time in this study showing significant day night variation in SCN, pineal and SN may prove useful towards targeting novel treatments for circadian dysfunction, good health and longevity.

Variability of soccer referees' match performances.

PubMed

Weston, M; Drust, B; Atkinson, G; Gregson, W

2011-03-01

The aim of the present study was to determine the between-match variability in soccer referees' match performances. 1 269 individual match observations were undertaken on 59 referees (range 2-79 games per referee) officiating in the English Premier League and Championship from 2003/2004 to 2007/2008 using a computerised tracking system (Prozone (®), Leeds, England). Between-match coefficients of variation (CV) were calculated for all games and then compared between referee age and experience groups. High mean CVs were observed for high-speed running distance (25.9±10.1%), recovery time (32.7±13.8%), explosive sprints (34.3±16.6%), total number of sprints (54.0±20.7%) and number of match fouls (28±4.6%). Smaller CVs were observed for total distance covered (3.8±1.5%), top sprinting speed (5.6±10.9%), distance from the ball (4.2±1.9%) and the distance from fouls (9.9±4.3%). Variability in match activities was not influenced by referee age or experience. The present study's findings demonstrate that variability in soccer referees' match performances is high in some variables and not dependent on referee age or experience. Such variability means that research requires large sample sizes to detect real systematic changes in a number of performance characteristics when studied during matches. © Georg Thieme Verlag KG Stuttgart · New York.

Hunger and overweight in Canadian school-aged children: A propensity score matching analysis.

PubMed

Sentenac, Mariane; Gariepy, Geneviève; McKinnon, Britt; Elgar, Frank J

2016-12-27

The last decade saw a higher prevalence of overweight reported among food-insecure families in Canada, but no robust evidence exists on the covariate-adjusted association in children. In this study, we examined the association between hunger and overweight in Canadian students, using a propensity score matching analysis to reduce confounding. This research used data from the 2009/2010 Canadian Health Behaviour in School-aged Children study on a representative national sample of students in Grades 6 through 10. Students self-reported their height and weight and how often they have gone to school or to bed hungry due to a lack of food at home. Multivariate logistic regression modeling was conducted on the total sample (N = 17,694) and on the sample matched on propensity scores (n = 7,788). The overall prevalence of overweight among students was 20.2% with a significant difference between students who reported hunger (24.0%; 95% CI: 22.1-26.0) and students who did not (19.0%; 95% CI: 17.9-20.2). Analysis on the matched sample revealed a significant association between hunger and overweight in children (adjusted odds ratio: 1.30; 95% CI: 1.12-1.50). A substantial number of Canadian students have reported being hungry because of a lack of food at home. These students are at increased risk of overweight, regardless of their social class. Child hunger and household food insecurity exist in Canada and constitute a call for policy action at a national level.

Comparison of Conditioning Impairments in Children with Down Syndrome, Autistic Spectrum Disorders and Mental Age-Matched Controls

ERIC Educational Resources Information Center

Reed, P.; Staytom, L.; Stott, S.; Truzoli, R.

2011-01-01

Background: This study investigated the relative ease of learning across four tasks suggested by an adaptation of Thomas's hierarchy of learning in children with Down syndrome, autism spectrum disorders and mental age-matched controls. Methods: Learning trials were carried out to investigate observational learning, instrumental learning, reversal…

Comparison of MRI-defined back muscles volume between patients with ankylosing spondylitis and control patients with chronic back pain: age and spinopelvic alignment matched study.

PubMed

Bok, Doo Hee; Kim, Jihye; Kim, Tae-Hwan

2017-02-01

To compare MRI-defined back muscle volume between AS patients and age, and spinopelvic alignment matched control patients with chronic back pain. 51 male patients with AS were enrolled. Age and spinopelvic alignment matched controls (male) were found among non-AS patients with chronic back pain. After matching procedure, fully matched controls were found in 31 of 51 AS patients (60.8%), who represent AS patients without deformity. However, matched controls were not found in 20 of 51 AS patients (39.2%), who represent AS patients with deformity. MRI parameters of back muscle (paraspinal muscle and psoas muscle) at L4/5 disc level including cross-sectional area (CSA) and fat-free cross-sectional area (FCSA) were compared between AS patients and matched controls. Covariates, including BMI, self-reported physical activity, and the presence of chronic disease, which can influence back muscle volume, were also investigated. There were no statistical differences in age, body mass index, score of back pain (NRS), and spinopelvic alignment, and physical activity between matched AS patients and control patients except for duration of back pain. All MRI parameters for paraspinal muscle volume in matched AS patients (without deformity) were significantly less than those of control patients, and significantly larger than those of non-matched AS patients (with deformity). Body size adjusted MRI parameters (relative CSA and relative FCSA) of paraspinal muscle showed strong correlations with lumbar lordosis and sacral slope. Such relationship between paraspinal muscle and spinopelvic parameters remained significant even after multivariate adjustment. AS patients without deformity already have decreased paraspinal muscle volume compared with age and spinopelvic alignment matched non-AS patients with chronic back pain. Such decrease in paraspinal muscle volume was significantly associated with kyphotic deformity of AS patients even after multivariate adjustment. Although the result

Environmental enrichment as a therapeutic avenue for anxiety in aged Wistar rats: Effect on cat odor exposition and GABAergic interneurons.

PubMed

Sampedro-Piquero, P; Castilla-Ortega, E; Zancada-Menendez, C; Santín, L J; Begega, A

2016-08-25

The use of more ethological animal models to study the neurobiology of anxiety has increased in recent years. We assessed the effect of an environmental enrichment (EE) protocol (24h/day over a period of two months) on anxiety-related behaviors when aged Wistar rats (21months old) were confronted with cat odor stimuli. Owing to the relationship between GABAergic interneurons and the anxiety-related neuronal network, we examined changes in the expression of Parvalbumin (PV) and 67kDa form of glutamic acid decarboxylase (GAD-67) immunoreactive cells in different brain regions involved in stress response. Behavioral results revealed that enriched rats traveled further and made more grooming behaviors during the habituation session. In the cat odor session, they traveled longer distances and they showed more active interaction with the odor stimuli and less time in freezing behavior. Zone analysis revealed that the enriched group spent more time in the intermediate zone according to the proximity of the predator odor. Regarding the neurobiological data, the EE increased the expression of PV-positive cells in some medial prefrontal regions (cingulate (Cg) and prelimbic (PL) cortices), whereas the GAD-67 expression in the basolateral amygdala was reduced in the enriched group. Our results suggest that EE is able to reduce anxiety-like behaviors in aged animals even when ethologically relevant stimuli are used. Moreover, GABAergic interneurons could be involved in mediating this resilient behavior. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

SYSTEMIC IMBALANCE OF ESSENTIAL METALS AND CARDIAC GENE EXPRESSION IN RATS FOLLOWING ACUTE PULMONARY ZINC EXPOSURE

EPA Science Inventory

We have recently demonstrated that PM containing water-soluble zinc may cause cardiac injury following pulmonary exposure. To investigate if pulmonary zinc exposure causes systemic metal imbalance and direct cardiac effects, we intratracheally (IT) instilled male Wistar Kyoto (WK...

Analysis of the Impacts of an Early Start for Compliance with the Kyoto Protocol

EIA Publications

1999-01-01

This report describes the Energy Information Administration's analysis of the impacts of an early start, using the same methodology as in Impacts of the Kyoto Protocol on U.S. Energy Markets and Economic Activity, with only those changes in assumptions caused by the early start date.

Prophylactic effects of elastin peptide derived from the bulbus arteriosus of fish on vascular dysfunction in spontaneously hypertensive rats.

PubMed

Takemori, Kumiko; Yamamoto, Ei; Ito, Hiroyuki; Kometani, Takashi

2015-01-01

To determine the prophylactic effects of an elastin peptide derived from the bulbus arteriosus of bonitos and prolylglycine (PG), a degradation product of elastin peptide, on vascular dysfunction in spontaneously hypertensive rats (SHRs). Male 15-week-old SHR/Izm rats were fed without (control group) or with elastin peptide (1 g/kg body weight) for 5 weeks (EP group), or were infused via an osmotic mini-pump for 4 weeks with PG (PG group) or saline (control group). Using thoracic aortas, we assessed endothelial changes by scanning electron microscopy. Vascular reactivity (contraction and relaxation) and pressure-induced distension was compared. mRNA production levels of endothelial nitric oxide synthase (eNOS) and intercellular adhesion molecule-1 (ICAM-1) were investigated by real-time-polymerase chain reaction. Aortas of the EP group displayed limited endothelial damage compared with that in the control group. Under treatment of SHRs with elastin peptide, the effect of phenylephrine returned closer to the normal level observed in normotensive Wistar-Kyoto (WKY/Izm) rats. mRNA production of eNOS (but not ICAM-1) was greater in the EP group than in the control group. Endothelial damage was suppressed and pressure-induced vascular distension was greater in the PG group than in the corresponding control group. These results suggest that elastin peptide from bonitos elicits prophylactic affects hypertension-associated vascular dysfunction by targeting the eNOS signaling pathway. PG may be a key mediator of the beneficial effects of elastin peptide. Copyright © 2014 Elsevier Inc. All rights reserved.

Extracellular levels of lactate, but not oxygen, reflect sleep homeostasis in the rat cerebral cortex.

PubMed

Dash, Michael B; Tononi, Giulio; Cirelli, Chiara

2012-07-01

It is well established that brain metabolism is higher during wake and rapid eye movement (REM) sleep than in nonrapid eye movement (NREM) sleep. Most of the brain's energy is used to maintain neuronal firing and glutamatergic transmission. Recent evidence shows that cortical firing rates, extracellular glutamate levels, and markers of excitatory synaptic strength increase with time spent awake and decline throughout NREM sleep. These data imply that the metabolic cost of each behavioral state is not fixed but may reflect sleep-wake history, a possibility that is investigated in the current report. Chronic (4d) electroencephalographic (EEG) recordings in the rat cerebral cortex were coupled with fixed-potential amperometry to monitor the extracellular concentration of oxygen ([oxy]) and lactate ([lac]) on a second-by-second basis across the spontaneous sleep-wake cycle and in response to sleep deprivation. Basic sleep research laboratory. Wistar Kyoto (WKY) adult male rats. N/A. Within 30-60 sec [lac] and [oxy] progressively increased during wake and REM sleep and declined during NREM sleep (n = 10 rats/metabolite), but with several differences. [Oxy], but not [lac], increased more during wake with high motor activity and/or elevated EEG high-frequency power. Meanwhile, only the NREM decline of [lac] reflected sleep pressure as measured by slow-wave activity, mirroring previous results for cortical glutamate. The observed state-dependent changes in cortical [lac] and [oxy] are consistent with higher brain metabolism during waking and REM sleep in comparison with NREM sleep. Moreover, these data suggest that glycolytic activity, most likely through its link with glutamatergic transmission, reflects sleep homeostasis.

Impulsiveness, overactivity, and poorer sustained attention improve by chronic treatment with low doses of l-amphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD).

PubMed

Sagvolden, Terje

2011-03-30

ADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR), shows pronounced overactivity, impulsiveness, and deficient sustained attention. The primary objective of the present research was to investigate behavioral effects of a range of doses of chronic l-amphetamine on ADHD-like symptoms in the SHR. The present study tested the behavioral effects of 0.75 and 2.2 mg l-amphetamine base/kg i.p. in male SHRs and their controls, the Wistar Kyoto rat (WKY). ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness. The striking impulsiveness, overactivity, and poorer sustained attention seen during baseline conditions in the SHR were improved by chronic treatment with l-amphetamine. The dose-response curves were, however, different for the different behaviors. Most significantly, the 0.75 mg/kg dose of l-amphetamine improved sustained attention without reducing overactivity and impulsiveness. The 2.2 mg/kg dose improved sustained attention as well as reduced SHR overactivity and impulsiveness. The effects of l-amphetamine to reduce the behavioral symptoms of ADHD in the SHR were maintained over the 14 days of daily dosing with no evidence of tolerance developing.

Antihypertensive treatment differentially affects vascular sphingolipid biology in spontaneously hypertensive rats.

PubMed

Spijkers, Léon J A; Janssen, Ben J A; Nelissen, Jelly; Meens, Merlijn J P M T; Wijesinghe, Dayanjan; Chalfant, Charles E; De Mey, Jo G R; Alewijnse, Astrid E; Peters, Stephan L M

2011-01-01

We have previously shown that essential hypertension in humans and spontaneously hypertensive rats (SHR), is associated with increased levels of ceramide and marked alterations in sphingolipid biology. Pharmacological elevation of ceramide in isolated carotid arteries of SHR leads to vasoconstriction via a calcium-independent phospholipase A(2), cyclooxygenase-1 and thromboxane synthase-dependent release of thromboxane A(2). This phenomenon is almost absent in vessels from normotensive Wistar Kyoto (WKY) rats. Here we investigated whether lowering of blood pressure can reverse elevated ceramide levels and reduce ceramide-mediated contractions in SHR. For this purpose SHR were treated for 4 weeks with the angiotensin II type 1 receptor antagonist losartan or the vasodilator hydralazine. Both drugs decreased blood pressure equally (SBP untreated SHR: 191±7 mmHg, losartan: 125±5 mmHg and hydralazine: 113±14 mmHg). The blood pressure lowering was associated with a 20-25% reduction in vascular ceramide levels and improved endothelial function of isolated carotid arteries in both groups. Interestingly, losartan, but not hydralazine treatment, markedly reduced sphingomyelinase-induced contractions. While both drugs lowered cyclooxygenase-1 expression, only losartan and not hydralazine, reduced the endothelial expression of calcium-independent phospholipase A(2). The latter finding may explain the effect of losartan treatment on sphingomyelinase-induced vascular contraction. In summary, this study corroborates the importance of sphingolipid biology in blood pressure control and specifically shows that blood pressure lowering reduces vascular ceramide levels in SHR and that losartan treatment, but not blood pressure lowering per se, reduces ceramide-mediated arterial contractions.

Aerobic exercise reduces oxidative stress and improves vascular changes of small mesenteric and coronary arteries in hypertension

PubMed Central

Roque, Fernanda R; Briones, Ana M; García-Redondo, Ana B; Galán, María; Martínez-Revelles, Sonia; Avendaño, Maria S; Cachofeiro, Victoria; Fernandes, Tiago; Vassallo, Dalton V; Oliveira, Edilamar M; Salaices, Mercedes

2013-01-01

Background and Purpose Regular physical activity is an effective non-pharmacological therapy for prevention and control of hypertension. We investigated the effects of aerobic exercise training in vascular remodelling and in the mechanical and functional alterations of coronary and small mesenteric arteries from spontaneously hypertensive rats (SHR). Experimental Approach Normotensive Wistar Kyoto (WKY), SHR and SHR trained on a treadmill for 12 weeks were used to evaluate vascular structural, mechanical and functional properties. Key Results Exercise did not affect lumen diameter, wall thickness and wall/lumen ratio but reduced vascular stiffness of coronary and mesenteric arteries from SHR. Exercise also reduced collagen deposition and normalized altered internal elastic lamina organization and expression of MMP-9 in mesenteric arteries from SHR. Exercise did not affect contractile responses of coronary arteries but improved the endothelium-dependent relaxation in SHR. In mesenteric arteries, training normalized the increased contractile responses induced by U46619 and by high concentrations of acetylcholine. In vessels from SHR, exercise normalized the effects of the NADPH oxidase inhibitor apocynin and the NOS inhibitor l-NAME in vasodilator or vasoconstrictor responses, normalized the increased O2− production and the reduced Cu/Zn superoxide dismutase expression and increased NO production. Conclusions and Implications Exercise training of SHR improves endothelial function and vascular stiffness in coronary and small mesenteric arteries. This might be related to the concomitant decrease of oxidative stress and increase of NO bioavailability. Such effects demonstrate the beneficial effects of exercise on the vascular system and could contribute to a reduction in blood pressure. PMID:22994554

Dynamic exercise training prevents exercise pressor reflex overactivity in spontaneously hypertensive rats

PubMed Central

Iwamoto, Gary A.; Vongpatanasin, Wanpen; Mitchell, Jere H.; Smith, Scott A.

2015-01-01

Cardiovascular responses to exercise are exaggerated in hypertension. We previously demonstrated that this heightened cardiovascular response to exercise is mediated by an abnormal skeletal muscle exercise pressor reflex (EPR) with important contributions from its mechanically and chemically sensitive components. Exercise training attenuates exercise pressor reflex function in healthy subjects as well as in heart failure rats. However, whether exercise training has similar physiological benefits in hypertension remains to be elucidated. Thus we tested the hypothesis that the EPR overactivity manifest in hypertension is mitigated by exercise training. Changes in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in response to muscle contraction, passive muscle stretch, and hindlimb intra-arterial capsaicin administration were examined in untrained normotensive Wistar-Kyoto rats (WKYUT; n = 6), exercise-trained WKY (WKYET; n = 7), untrained spontaneously hypertensive rats (SHRUT; n = 8), and exercise-trained SHR (SHRET; n = 7). Baseline MAP after decerebration was significantly decreased by 3 mo of wheel running in SHRET (104 ± 9 mmHg) compared with SHRUT (125 ± 10 mmHg). As previously reported, the pressor and renal sympathetic responses to muscle contraction, stretch, and capsaicin administration were significantly higher in SHRUT than WKYUT. Exercise training significantly attenuated the enhanced contraction-induced elevations in MAP (SHRUT: 53 ± 11 mmHg; SHRET: 19 ± 3 mmHg) and RSNA (SHRUT: 145 ± 32%; SHRET: 57 ± 11%). Training produced similar attenuating effects in SHR during passive stretch and capsaicin administration. These data demonstrate that the abnormally exaggerated EPR function that develops in hypertensive rats is significantly diminished by exercise training. PMID:26163445

Aerobic exercise reduces oxidative stress and improves vascular changes of small mesenteric and coronary arteries in hypertension.

PubMed

Roque, Fernanda R; Briones, Ana M; García-Redondo, Ana B; Galán, María; Martínez-Revelles, Sonia; Avendaño, Maria S; Cachofeiro, Victoria; Fernandes, Tiago; Vassallo, Dalton V; Oliveira, Edilamar M; Salaices, Mercedes

2013-02-01

Regular physical activity is an effective non-pharmacological therapy for prevention and control of hypertension. We investigated the effects of aerobic exercise training in vascular remodelling and in the mechanical and functional alterations of coronary and small mesenteric arteries from spontaneously hypertensive rats (SHR). Normotensive Wistar Kyoto (WKY), SHR and SHR trained on a treadmill for 12 weeks were used to evaluate vascular structural, mechanical and functional properties. Exercise did not affect lumen diameter, wall thickness and wall/lumen ratio but reduced vascular stiffness of coronary and mesenteric arteries from SHR. Exercise also reduced collagen deposition and normalized altered internal elastic lamina organization and expression of MMP-9 in mesenteric arteries from SHR. Exercise did not affect contractile responses of coronary arteries but improved the endothelium-dependent relaxation in SHR. In mesenteric arteries, training normalized the increased contractile responses induced by U46619 and by high concentrations of acetylcholine. In vessels from SHR, exercise normalized the effects of the NADPH oxidase inhibitor apocynin and the NOS inhibitor l-NAME in vasodilator or vasoconstrictor responses, normalized the increased O(2) (-) production and the reduced Cu/Zn superoxide dismutase expression and increased NO production. Exercise training of SHR improves endothelial function and vascular stiffness in coronary and small mesenteric arteries. This might be related to the concomitant decrease of oxidative stress and increase of NO bioavailability. Such effects demonstrate the beneficial effects of exercise on the vascular system and could contribute to a reduction in blood pressure. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Impulsiveness, overactivity, and poorer sustained attention improve by chronic treatment with low doses of l-amphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD)

PubMed Central

2011-01-01

Background ADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR), shows pronounced overactivity, impulsiveness, and deficient sustained attention. The primary objective of the present research was to investigate behavioral effects of a range of doses of chronic l-amphetamine on ADHD-like symptoms in the SHR. Methods The present study tested the behavioral effects of 0.75 and 2.2 mg l-amphetamine base/kg i.p. in male SHRs and their controls, the Wistar Kyoto rat (WKY). ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness. Results The striking impulsiveness, overactivity, and poorer sustained attention seen during baseline conditions in the SHR were improved by chronic treatment with l-amphetamine. The dose-response curves were, however, different for the different behaviors. Most significantly, the 0.75 mg/kg dose of l-amphetamine improved sustained attention without reducing overactivity and impulsiveness. The 2.2 mg/kg dose improved sustained attention as well as reduced SHR overactivity and impulsiveness. Discussion The effects of l-amphetamine to reduce the behavioral symptoms of ADHD in the SHR were maintained over the 14 days of daily dosing with no evidence of tolerance developing. PMID:21450079

Outcomes of hip arthroscopy in patients aged 50 years or older compared with a matched-pair control of patients aged 30 years or younger.

PubMed

Domb, Benjamin G; Linder, Dror; Finley, Zachary; Botser, Itamar B; Chen, Austin; Williamson, Joseph; Gupta, Asheesh

2015-02-01

Age has been suggested as a negative prognostic factor for hip arthroscopy. The purpose of this study was to compare patient characteristics and outcomes after hip arthroscopy in patients aged 50 years or older with a matched control group of patients aged 30 years or younger at a minimum postoperative follow-up of 2 years. Between September 2008 and March 2010, data were prospectively collected on all patients aged 50 years or older undergoing primary hip arthroscopy. Fifty-two patients met our inclusion and matching criteria, of whom all 52 (100%) were available for follow-up at a minimum of 2 years. This cohort was compared with a matched-pair control group of patients aged 30 years or younger who underwent similar procedures. The mean age of the study group was 54.8 years (range, 50 to 69 years), and that of the control group was 20.3 years (range, 13 to 30 years). The groups were matched at a 1:1 ratio, including 18 male patients (34.6%) and 34 female patients (65.4%) in each group, with a mean follow-up period of 32 months (range, 24 to 54 months). In the younger control group, the score improvement from preoperatively to 2 years' follow-up was 62.9 to 84.2 for the modified Harris Hip Score, 60.5 to 84.2 for the Non-Arthritic Hip Score, 63.1 to 86.5 for the Hip Outcome Score-Activities of Daily Living, and 42.2 to 72.7 for the Hip Outcome Score-Sport-Specific Subscale. In the older study group, the score improvement from preoperatively to 2 years' follow-up was 61.2 to 82.2 for the modified Harris Hip Score, 59.9 to 80.4 for the Non-Arthritic Hip Score, 63.9 to 83 for the Hip Outcome Score-Activities of Daily Living, and 41.2 to 64.6 for the Hip Outcome Score-Sport-Specific Subscale. All improvements in both groups were statistically significant at the 2-year postoperative follow-up (P < .001). There was no significant difference for all patient-reported outcome (PRO) scores at final follow-up between both groups. When we compared the change in PRO scores (�

Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats#

EPA Science Inventory

Acute ozone exposure increases circulating stress hormones and induces metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for both ozone-induced metabolic effects and lung injury. Male Wistar-Kyoto rats ...

RNA interference targeting the ACE gene reduced blood pressure and improved myocardial remodelling in SHRs.

PubMed

He, Junhua; Bian, Yunfei; Gao, Fen; Li, Maolian; Qiu, Ling; Wu, Weidong; Zhou, Hua; Liu, Gaizhen; Xiao, Chuanshi

2009-02-01

The purpose of the present study was to investigate the effects on blood pressure and myocardial hypertrophy in SHRs (spontaneously hypertensive rats) of RNAi (RNA interference) targeting ACE (angiotensin-converting enzyme). SHRs were treated with normal saline as vehicle controls, with Ad5-EGFP as vector controls, and with recombinant adenoviral vectors Ad5-EGFP-ACE-shRNA, carrying shRNA (small hairpin RNA) for ACE as ACE-RNAi. WKY (Wistar-Kyoto) rats were used as normotensive controls treated with normal saline. The systolic blood pressure of the caudal artery was recorded. Serum levels of ACE and AngII (angiotensin II) were determined using ELISA. ACE mRNA and protein levels were determined in aorta, myocardium, kidney and lung. On day 32 of the experiment, the heart was pathologically examined. The ratios of heart weight/body weight and left ventricular weight/body weight were calculated. The serum concentration of ACE was lower in ACE-RNAi rats (16.37+/-3.90 ng/ml) compared with vehicle controls and vector controls (48.26+/-1.50 ng/ml and 46.67+/-2.82 ng/ml respectively; both P<0.05), but comparable between ACE-RNAi rats and WKY rats (14.88+/-3.15 ng/ml; P>0.05). The serum concentration of AngII was also significantly lower in ACE-RNAi rats (18.24+/-3.69 pg/ml) compared with vehicle controls and vector controls (46.21+/-5.06 pg/ml and 44.93+/-4.12 pg/ml respectively; both P<0.05), but comparable between ACE-RNAi rats and WKY rats (16.06+/-3.11 pg/ml; P>0.05). The expression of ACE mRNA and ACE protein were significantly reduced in the myocardium, aorta, kidney and lung in ACE-RNAi rats compared with that in vehicle controls and in vector controls (all P<0.05). ACE-RNAi treatment resulted in a reduction in systolic blood pressure by 22+/-3 mmHg and the ACE-RNAi-induced reduction lasted for more than 14 days. In contrast, blood pressure was continuously increased in the vehicle controls as well as in the vector controls. The ratios of heart weight/body weight

Stevia preferences in Wistar rats.

PubMed

Núñez Martínez, Paula; Argüelles Luis, Juan; Perillán Méndez, Carmen

2016-11-01

The Stevia rebaudiana plant is likely to become a major source of high-potency sweetener for the growing natural-food market. S. rebaudiana is the source of a number of sweet diterpenoid glycosides, but the major sweet constituents are rebaudioside A and stevioside. These two constituents have similar pharmacokinetic and metabolic profiles in rats and humans, and thus, studies carried out with either steviol glycoside are relevant to both. Other studies illustrate the diversity of voluntary sweet intake in mammals. This study was done using a series of two-bottle tests that compared a wide range of sweetener concentrations versus saccharin concentrations and versus water. Wistar rats displayed preferences for stevia extract and pure rebaudioside A solutions over water at a range of concentrations (0.001% to 0.3%), and their intake peak occurred at 0.1% concentration. They also preferred solutions prepared with a commercial rebaudioside A plus erythritol mixture to water, and their peak was at 2% concentration. The present study provides new information about the responses of Wistar rats to stevia compounds and commercial stevia products such as Truvia. These results could help with the appropriate dosage selection for focused behavioral and physiological studies on stevia.

[Prof. Michiharu Matsuoka, founder of the Department of Orthopaedic Surgery, Kyoto University, and his achievements in orthopaedic surgery in the Meiji Era of Japan (part 1: establishment of the department)].

PubMed

Hirotani, Hayato

2005-09-01

The Department of Orthopaedic and Musculoskeletal Surgery, Graduate School of Medicine, Kyoto University (formerly the Department of Orthopaedic Surgery, Kyoto Medical School, Kyoto Imperial University) was founded by Imperial Ordinance, Article No. 89 issued on April 23, 1906. On May 4, 1906, Dr. Shinichiro Asahara, Assistant Professor of the Department of Surgery, was appointed as the first director of the Department of Orthopaedic Surgery, Kyoto Medical School, Kyoto Imperial University. Dr. Michiharu Matsuoka, Assistant Doctor of the Department of Surgery, Tokyo Medical School, Imperial University of Tokyo, was appointed Assistant Professor of Surgery, Kyoto Medical School, Kyoto Imperial University in March 1901. From August 1903 to May 1906, he studied orthopaedic surgery in Germany and returned on May 5, 1906. Dr. Matsuoka was appointed as the director and chief of the Department on May 13, 1906 and took over Dr. Asahara's position. On June 18, 1906, Dr. Matsuoka started his clinic and began giving lectures on orthopaedic surgery. This was the first department of orthopaedic surgery among the Japanese medical schools. Dr. Matsuoka was appointed as Professor in 1907. He had to overcome several obstacles to establish the medical department of a new discipline that had never existed in Japanese medical schools. This article discusses Dr. Matsuoka's contributions to establishing and developing orthopaedic surgery in Japan in the Meiji-era.

Late-onset dietary restriction compensates for age-related increase in oxidative stress and alterations of HSP 70 and synapsin 1 protein levels in male Wistar rats.

PubMed

Sharma, Sandeep; Singh, Rumani; Kaur, Manpreet; Kaur, Gurcharan

2010-04-01

Numerous reports implicate increased oxidative stress in the functional and structural changes occurring in the brain and other organs as a part of the normal aging process. Dietary restriction (DR) has long been shown to be life-prolonging intervention in several species. This study was aimed to assess the potential efficacy of late-onset short term DR when initiated in 21 months old male wistar rats for 3 months on the antioxidant defense system and lipid peroxidation, cellular stress response protein HSP 70 and synaptic marker protein synapsin 1 in discrete brain regions such as cortex, hypothalamus, and hippocampus as well as liver, kidney and heart from 24 month old rats. Age-associated decline in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione, and elevated levels of lipid peroxidation was observed in brain and peripheral organ as well as increased expression of HSP 70 and reduction in synapsin 1 was observed in brain studied. Late-onset short term DR was effective in partially restoring the antioxidant status and in decreasing lipid peroxidation level as well as enhancing the expression of HSP 70 and synapsin 1 in aged rats. Late onset short term DR also prevented age-related neurodegeneration as revealed by Fluoro-Jade B staining in hippocampus and cortex regions of rat brain. Thus our current results suggest that DR initiated even in old age has the potential to improve age related decline in body functions.

Association of young and advanced age of pregnant women with the risk of isolated congenital abnormalities in Hungary - a population-based case-matched control study.

PubMed

Csermely, Gyula; Susánszky, Éva; Czeizel, Andrew E

2015-03-01

To analyze the possible association of maternal age with the risk of all congenital abnormalities (CAs) in a population-based large case-matched control data set. The Hungarian Case-Control Surveillance of Congenital Abnormalities included 21,494 cases with isolated CA and their 34,311 matched controls. First the distribution of maternal age groups in 24 CA-groups and their matched controls was compared. In the second step, young (19 years or less) and advanced (35 years or more) age groups were compared. Finally, the subgroups of neural-tube defects, congenital heart defects and abdominal wall's CA were evaluated separately. A higher risk of gastroschisis, congenital heart defects, particularly left-sided obstructive defects, undescended testis and clubfoot was found in the youngest age group (19 years or less) of cases. The higher proportion of pregnant women with advanced age (i.e. 35 years or more) showed only a borderline excess in cases with clubfoot. The so-called U-shaped risk of maternal age distribution was found in cases with clubfoot and in the total group of isolated CAs. The maternal age is a contributing factor to the origin of some isolated CAs mainly in young pregnant women.

Pediatric MATCH Infographic

Cancer.gov

Infographic explaining NCI-COG Pediatric MATCH, a cancer treatment clinical trial for children and adolescents, from 1 to 21 years of age, that is testing the use of precision medicine for pediatric cancers.

NOVEL INSIGHTS INTO THE MECHANISM OF SUBCHRONIC AIR POLLUTANT-INDUCED CARDIOVASCULAR IMPAIRMENT

EPA Science Inventory

The mechanisms by which air pollutants induce cardiovascular mortality are unknown. We hypothesized that blood vessels are the target of injury by circulating oxidation by-products following pollutant exposure. We exposed male Wistar Kyoto rats (12-15 wks old), nose-only to air, ...

Allometric relationships among body mass, MUZZLE-tail length, and tibia length during the growth of Wistar rats.

PubMed

Santiago, Hildemberg Agostinho Rocha de; De Pierro, Lucas Rodolfo; Reis, Rafael Menezes; Caluz, Antônio Gabriel Ricardo Engracia; Ribeiro, Victor Barbosa; Volpon, José Batista

2015-11-01

To investigate allometric relationships among body mass (BM), muzzle-tail length (MTL), and tibia length (TL) in Wistar rats and establish their growth rate change parameters. Eighteen male and 18 female Wistar rats were studied from the 3rd to the 21st week of age. BM, MTL, and TL were measured daily, and relative growth was compared using allometry. A positive correlation between BM and MTL (p<0.05) and BM and TL (p<0.05) was observed. Males and females showed comparable curves; however, females had turning points at a younger age. The allometric relationship between BM and MTL presented a regular increase until reaching a mass of 351 g (males) and 405 g (females). BM and TL showed an initial increase until 185 g (males) and 182 g (females), and then reached a plateau that finished at 412 g (males) and 334 g (females), to display another increase. The allometric relationship of body mass with animal length and tibia length was comparable for male and female rats, with female rats maturing earlier. Animal longitudinal growth occurred in a single stage. In contrast, tibia length depicted two stages of accelerated growth with an intermediate period of deceleration.

Developmental stress elicits preference for methamphetamine in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder.

PubMed

Womersley, Jacqueline S; Mpeta, Bafokeng; Dimatelis, Jacqueline J; Kellaway, Lauriston A; Stein, Dan J; Russell, Vivienne A

2016-06-17

Developmental stress has been hypothesised to interact with genetic predisposition to increase the risk of developing substance use disorders. Here we have investigated the effects of maternal separation-induced developmental stress using a behavioural proxy of methamphetamine preference in an animal model of attention-deficit/hyperactivity disorder, the spontaneously hypertensive rat, versus Wistar Kyoto and Sprague-Dawley comparator strains. Analysis of results obtained using a conditioned place preference paradigm revealed a significant strain × stress interaction with maternal separation inducing preference for the methamphetamine-associated compartment in spontaneously hypertensive rats. Maternal separation increased behavioural sensitization to the locomotor-stimulatory effects of methamphetamine in both spontaneously hypertensive and Sprague-Dawley strains but not in Wistar Kyoto rats. Our findings indicate that developmental stress in a genetic rat model of attention-deficit/hyperactivity disorder may foster a vulnerability to the development of substance use disorders.

Clinical and Demographic Evaluation of a Holoprosencephaly Cohort From the Kyoto Collection of Human Embryos.

PubMed

Abe, Yu; Kruszka, Paul; Martinez, Ariel F; Roessler, Erich; Shiota, Kohei; Yamada, Shigehito; Muenke, Maximilian

2018-06-01

Holoprosencephaly (HPE) is a genetically and phenotypically heterogeneous disorder involving developmental defects. HPE is a rare condition (1/10,000-20,000 newborns) but can be found as frequently as 1/250 among conceptions, suggesting that most HPE embryos are incompatible with postnatal life and result in spontaneous abortions during the first trimester of gestation. Beginning in 1961, the Kyoto University in Japan collected over 44,000 human conceptuses in collaboration with several hundred domestic obstetricians. Over 200 cases of HPE have been identified in the Kyoto collection, which represents the largest single cohort of HPE early stage embryo specimens. In this study, we present a comprehensive clinical and demographic evaluation of this HPE cohort prior to genomic analysis. The total percentage of the threatened abortion among HPE embryos in the Kyoto collection was 67%. Almost 20% of the women with embryos affected by HPE had experienced spontaneous miscarriage. In addition, there was a significant tendency that the mothers with HPE cases had fewer live births than the control. Moreover, in 70% of cases, the mother reported bleeding during pregnancy, a higher percentage than expected, indicating that most of the conceptions with HPE embryos tend to be terminated spontaneously. There were no differences in smoking between mothers with HPE affected and unaffected pregnancies; however, alcohol use was higher in women with pregnancies affected by HPE. In this study, we precisely characterize the phenotype and environmental influences of embryos affected by HPE allowing the future leveraging of genomic technologies to further understand the genetics of forebrain development. Anat Rec, 301:973-986, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Comparison of biomechanical gait parameters of young children with haemophilia and those of age-matched peers.

PubMed

Stephensen, D; Drechsler, W; Winter, M; Scott, O

2009-03-01

Quality of life for children with haemophilia has improved since the introduction of prophylaxis. The frequency of joint haemorrhages has reduced, but the consequences of reduced bleeding on the biomechanical parameters of walking are not well understood. This study explored the differences in sagittal plane biomechanics of walking between a control group (Group 1) of normal age-matched children and children with haemophilia (Group 2) with a target ankle joint. A motion capture system and two force platforms were used to collect sagittal plane kinematic, kinetic and temporal-spatial data during walking of 14 age-matched normal children and 14 children with haemophilia aged 7-13 years. Group differences in maximum and minimum flexion/extension angles and moments of the hip, knee and ankle joints, ground reaction forces and temporal-spatial gait cycle parameters were analysed using one-way anova. Significant changes (P < 0.05) in kinematic and kinetic parameters but not temporal-spatial parameters were found in children with haemophilia; greater flexion angles and external moments of force at the knee, greater ankle plantarflexion external moments and lower hip flexion external moments. These results suggest that early biomechanical changes are present in young haemophilic children with a history of a target ankle joint and imply that lower limb joint function is more impaired than current clinical evaluations indicate. Protocols and quantitative data on the biomechanical gait pattern of children with haemophilia reported in this study provide a baseline to evaluate lower limb joint function and clinical progression.

An augmented CO2 chemoreflex and overactive orexin system are linked with hypertension in young and adult spontaneously hypertensive rats.

PubMed

Li, Aihua; Roy, Sarah H; Nattie, Eugene E

2016-09-01

Activation of central chemoreceptors by CO2 increases sympathetic nerve activity (SNA), arterial blood pressure (ABP) and breathing. These effects are exaggerated in spontaneously hypertensive rats (SHRs), resulting in an augmented CO2 chemoreflex that affects both breathing and ABP. The augmented CO2 chemoreflex and the high ABP are measureable in young SHRs (postnatal day 30-58) and become greater in adult SHRs. Blockade of orexin receptors can normalize the augmented CO2 chemoreflex and the high ABP in young SHRs and normalize the augmented CO2 chemoreflex and significantly lower the high ABP in adult SHRs. In the hypothalamus, SHRs have more orexin neurons, and a greater proportion of them increase their activity with CO2 . The orexin system is overactive in SHRs and contributes to the augmented CO2 chemoreflex and hypertension. Modulation of the orexin system may be beneficial in the treatment of neurogenic hypertension. Activation of central chemoreceptors by CO2 increases arterial blood pressure (ABP), sympathetic nerve activity and breathing. In spontaneously hypertensive rats (SHRs), high ABP is associated with enhanced sympathetic nerve activity and peripheral chemoreflexes. We hypothesized that an augmented CO2 chemoreflex and overactive orexin system are linked with high ABP in both young (postnatal day 30-58) and adult SHRs (4-6 months). Our main findings are as follows. (i) An augmented CO2 chemoreflex and higher ABP in SHRs are measureable at a young age and increase in adulthood. In wakefulness, the ventilatory response to normoxic hypercapnia is higher in young SHRs (mean ± SEM: 179 ± 11% increase) than in age-matched normotensive Wistar-Kyoto rats (114 ± 9% increase), but lower than in adult SHRs (226 ± 10% increase; P < 0.05). The resting ABP is higher in young SHRs (122 ± 5 mmHg) than in age-matched Wistar-Kyoto rats (99 ± 5 mmHg), but lower than in adult SHRs (152 ± 4 mmHg; P < 0.05). (ii

Oxidized lipids and lipid-mediators are involved in cardiovascular injury induced by diesel exhaust particles and ozone

EPA Science Inventory

The mechanisms by which air pollutants induce cardiac and vascular injuries are unknown. We hypothesized that these injuries involve alterations in'aortic membrane lipids and lipid-mediators. We exposed male Wistar Kyoto rats (12-15 wk old), nose-only to air, ozone (03; 0.5 ppm),...

CARDIAC INJURY FROM LONG-TERM EPISODIC EXPOSURE TO PARTICULATE MATTER (PM): SOLUBLE COMPONENTS OR SOLID PARTICLES?

EPA Science Inventory

Long-term exposure to PM has been associated with cardiac injury in rats. The purpose of this study was to investigate if cardiac injury was due to soluble metals (i.e., zinc), insoluble PM, or pulmonary injury/inflammation. Male Wistar Kyoto rats (n=8) were exposed intratracheal...

CARDIAC INJURY FROM LONG TERM EPISODIC EXPOSURE TO PARTICULATE MATTER (PM): SOLUBLE COMPONENTS OR SOLID PARTICLES?

EPA Science Inventory

Long-term exposure to PM has been associated with cardiac injury in rats. The purpose of this study was to investigate if cardiac injury was due to soluble metals (i.e., zinc), insoluble PM, or pulmonary injury/inflammation. Male Wistar Kyoto rats (n=8) were exposed intratracheal...

Intake of key micronutrients and food groups in patients with late-stage age-related macular degeneration compared with age-sex-matched controls.

PubMed

Gopinath, Bamini; Liew, Gerald; Russell, Joanna; Cosatto, Victoria; Burlutsky, George; Mitchell, Paul

2017-08-01

Knowledge of the risk factor profile of patients presenting with late-stage age-related macular degeneration (AMD) could help identify the most frequent modifiable AMD precursors among people who are referred for treatment. We aimed to assess dietary behaviours by comparing adjusted mean intakes of micronutrients and major food groups (fruits, vegetables, fish) among patients with AMD and a sample of age-sex-matched controls. Cross-sectional analysis of 480 late AMD cases and 518 population-based age-sex-matched controls with no AMD signs. AMD cases (aged 60+ years) were those presenting for treatment to a hospital eye clinic in Sydney, Australia, during 2012-2015. The comparator group were obtained from a cohort study (Blue Mountains Eye Study; Sydney, Australia) during 2002-2009. Dietary intake was assessed using a semiquantitative food-frequency questionnaire. AMD lesions were assessed from retinal photographs. After multivariable adjustment, patients with late-stage AMD compared with controls had significantly lower intakes of vitamin E (7.4 vs 9.8 mg/day; p<0.0001), beta-carotene (6232 vs 7738 μg/day; p<0.0001), vitamin C (161 vs 184 mg/day; p=0.0002) and folate (498.3 vs 602 μg/day; p<0.0001); but had higher intakes of zinc (13.0 vs 11.9 mg/day; p<0.0001). A significantly lower proportion of patients with late AMD met the recommended intake of vegetables than controls: 52.9% versus 64.5%; p=0.0002. This study showed significant differences in intakes of vitamins C and E, beta-carotene, folate and vegetables between patients with late-stage AMD and healthy controls, and thus has provided a better understanding of the nutritional intake of patients presenting with advanced AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Remote Sensing and the Kyoto Protocol: A Review of Available and Future Technology for Monitoring Treaty Compliance

NASA Technical Reports Server (NTRS)

Imhoff, Marc L.; Rosenquist, A.; Milne, A. K.; Dobson, M. C.; Qi, J.

2000-01-01

An International workshop was held to address how remote sensing technology could be used to support the environmental monitoring requirements of the Kyoto Protocol. An overview of the issues addressed and the findings of the workshop are discussed.

Effects of cilazapril on the cerebral circulation in spontaneously hypertensive rats.

PubMed

Clozel, J P; Kuhn, H; Hefti, F

1989-12-01

Chronic hypertension is associated with a lower cerebral vascular reserve due to thickening of the media of cerebral vessels. The goal of the present study was to determine if long-term inhibition of angiotensin converting enzyme with cilazapril, a new long-acting angiotensin converting enzyme inhibitor, could improve cerebral vascular reserve. For this purpose, two groups of 12 spontaneously hypertensive rats were compared. One group was treated with 10 mg/kg/day cilazapril from 14 weeks to 33 weeks of age and was compared with a group treated with placebo. A third group of 12 Wistar-Kyoto rats treated with placebo was used as reference. At the end of the treatment period, cerebral vascular reserve was evaluated by measuring cerebral blood flow (radioactive microspheres) at rest and during maximal vasodilation induced by seizures provoked by bicuculline. Then, the rats were perfusion-fixed, and morphometry of the cerebral vasculature was performed. Cerebral vascular reserve was severely impaired in the spontaneously hypertensive rats since their maximal cerebral blood flow was decreased by 52% compared with the Wistar-Kyoto rats. Cilazapril normalized cerebral blood flow reserve. This normalization was associated with a decreased thickness of the medial layer in the carotid artery, the middle cerebral artery, and in the pial arteries larger than 100 microns. Further studies are required to determine whether this decreased medial thickness is due to the normalization of blood pressure induced by cilazapril or to the reduction of trophic factors such as angiotensin II.

[Climatic change and public health: scenarios after the coming into force of the Kyoto Protocol].

PubMed

Ballester, Ferran; Díaz, Julio; Moreno, José Manuel

2006-03-01

According to the reports of the intergovernmental panel for climatic change (IPCC) human beings of the present and near future are going to experiment, in fact we are already experimenting, important changes in the world climate. Conscious of the magnitude of the problem, international organizations have taken a series of initiatives headed to stop the climatic change and to reduce its impact. This willingness has been shaped into the agreements established in the Kyoto protocol, where countries commit to reduce greenhouse-effect gas emissions. Kyoto protocol has come into force on February 16th 2005 with the support of 141 signing countries. Among the major worries are the effects which climatic change may have upon health, such as: 1) changes in the morbidity- mortality related to temperature; 2) Effects on health related with extreme meteorological events (tornados, storms, hurricanes and extreme raining); 3) Air pollution and increase of associated health effects; d) Diseases transmitted by food and water and 4) Infectious diseases transmitted by vectors and by rodents. Even if all the countries in the world committed to the Kyoto Protocol, some consequences of the climatic change will be inevitable; among them some will have a negative impact on health. It would be necessary to adapt a key response strategy to minimize the impacts of climatic change and to reduce, at minimum cost, its adverse effects on health. From the Public Health position, a relevant role can and must be played concerning the understanding of the risks for health of such climatic changes, the design of surveillance systems to evaluate possible impacts, and the establishment of systems to prevent or reduce damages as well as the identification and development of investigation needs.

Use of virtual slide system for quick frozen intra-operative telepathology diagnosis in Kyoto, Japan.

PubMed

Tsuchihashi, Yasunari; Takamatsu, Terumasa; Hashimoto, Yukimasa; Takashima, Tooru; Nakano, Kooji; Fujita, Setsuya

2008-07-15

We started to use virtual slide (VS) and virtual microscopy (VM) systems for quick frozen intra-operative telepathology diagnosis in Kyoto, Japan. In the system we used a digital slide scanner, VASSALO by CLARO Inc., and a broadband optic fibre provided by NTT West Japan Inc. with the best effort capacity of 100 Mbps. The client is the pathology laboratory of Yamashiro Public Hospital, one of the local centre hospitals located in the south of Kyoto Prefecture, where a full-time pathologist is not present. The client is connected by VPN to the telepathology centre of our institute located in central Kyoto. As a result of the recent 15 test cases of VS telepathology diagnosis, including cases judging negative or positive surgical margins, we could estimate the usefulness of VS in intra-operative remote diagnosis. The time required for the frozen section VS file making was found to be around 10 min when we use x10 objective and if the maximal dimension of the frozen sample is less than 20 mm. Good correct focus of VS images was attained in all cases and all the fields of each tissue specimen. Up to now the capacity of best effort B-band appears to be sufficient to attain diagnosis on time in intra-operation. Telepathology diagnosis was achieved within 5 minutes in most cases using VS viewer provided by CLARO Inc. The VS telepathology system was found to be superior to the conventional still image telepathology system using a robotic microscope since in the former we can observe much greater image information than in the latter in a certain limited time of intra-operation and in the much more efficient ways. In the near future VS telepathology will replace conventional still image telepathology with a robotic microscope even in quick frozen intra-operative diagnosis.

Use of virtual slide system for quick frozen intra-operative telepathology diagnosis in Kyoto, Japan

PubMed Central

Tsuchihashi, Yasunari; Takamatsu, Terumasa; Hashimoto, Yukimasa; Takashima, Tooru; Nakano, Kooji; Fujita, Setsuya

2008-01-01

We started to use virtual slide (VS) and virtual microscopy (VM) systems for quick frozen intra-operative telepathology diagnosis in Kyoto, Japan. In the system we used a digital slide scanner, VASSALO by CLARO Inc., and a broadband optic fibre provided by NTT West Japan Inc. with the best effort capacity of 100 Mbps. The client is the pathology laboratory of Yamashiro Public hospital, one of the local centre hospitals located in the south of Kyoto Prefecture, where a fulltime pathologist is not present. The client is connected by VPN to the telepathology centre of our institute located in central Kyoto. As a result of the recent 15 test cases of VS telepathology diagnosis, including cases judging negative or positive surgical margins, we could estimate the usefulness of VS in intra-operative remote diagnosis. The time required for the frozen section VS file making was found to be around 10 min when we use ×10 objective and if the maximal dimension of the frozen sample is less than 20 mm. Good correct focus of VS images was attained in all cases and all the fields of each tissue specimen. Up to now the capacity of best effort B-band appears to be sufficient to attain diagnosis on time in intra-operation. Telepathology diagnosis was achieved within 5 minutes in most cases using VS viewer provided by CLARO Inc. The VS telepathology system was found to be superior to the conventional still image telepathology system using a robotic microscope since in the former we can observe much greater image information than in the latter in a certain limited time of intra-operation and in the much more efficient ways. In the near future VS telepathology will replace conventional still image telepathology with a robotic microscope even in quick frozen intra-operative diagnosis. PMID:18673520

Longitudinal development of match-running performance in elite male youth soccer players.

PubMed

Saward, C; Morris, J G; Nevill, M E; Nevill, A M; Sunderland, C

2016-08-01

This study longitudinally examined age-related changes in the match-running performance of retained and released elite youth soccer players aged 8-18 years. The effect of playing position on age-related changes was also considered. Across three seasons, 263 elite youth soccer players were assessed in 1-29 competitive matches (988 player-matches). For each player-match, total distance and distances covered at age group-specific speed zones (low-speed, high-speed, sprinting) were calculated using 1 Hz or 5 Hz GPS. Mixed modeling predicted that match-running performance developed nonlinearly, with age-related changes best described with quadratic age terms. Modeling predicted that playing position significantly modified age-related changes (P < 0.05) and retained players covered significantly more low-speed distance compared with released players (P < 0.05), by 75 ± 71 m/h (mean ± 95% CI; effect size ± 95% CI: 0.35 ± 0.34). Model intercepts randomly varied, indicating differences between players in match-running performance unexplained by age, playing position or status. These findings may assist experts in developing training programs specific to the match play demands of players of different ages and playing positions. Although retained players covered more low-speed distance than released players, further study of the actions comprising low-speed distance during match play is warranted to better understand factors differentiating retained and released players. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

ATRAZINE ALTERS STEROIDOGENESIS IN MALE WISTAR RATS

EPA Science Inventory

We have reported that atrazine (ATR, 200 mg/kg x 30 d) causes increased serum estrone (E) and estradiol (E2) in male wistar rats (Toxicol. Sci. 2000, 58:50-59). This study evaluates the short-term effects of ATR on E, E2 and their precursors in the steroidogenic pathway. Sixty-da...

Inhaled ozone (O3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats☆

PubMed Central

Miller, Desinia B.; Karoly, Edward D.; Jones, Jan C.; Ward, William O.; Vallanat, Beena D.; Andrews, Debora L.; Schladweiler, Mette C.; Snow, Samantha J.; Bass, Virginia L.; Richards, Judy E.; Ghio, Andrew J.; Cascio, Wayne E.; Ledbetter, Allen D.; Kodavanti, Urmila P.

2016-01-01

Air pollution has been linked to increased incidence of diabetes. Recently, we showed that ozone (O3) induces glucose intolerance, and increases serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that O3 exposure will cause systemic changes in metabolic homeostasis and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights. In the first experiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or O3 at 0.25, 0.50, or 1.0 ppm, 6 h/day for two days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0 ppm O3, 6 h/day for either one or two consecutive days, and systemic metabolic responses were determined immediately after or 18 h post-exposure. O3 increased serum glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18 h-post second exposure. O3 increased circulating metabolites of glycolysis, long-chain free fatty acids, branched-chain amino acids and cholesterol, while 1,5-anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycemic control, proteolysis and lipolysis. Liver gene expression increased for markers of glycolysis, TCA cycle and gluconeogenesis, and decreased for markers of steroid and fat biosynthesis. Genes involved in apoptosis and mitochondrial function were also impacted by O3. In conclusion, short-term O3 exposure induces global metabolic derangement involving glucose, lipid, and amino acid metabolism, typical of a stress–response. It remains to be examined if these alterations contribute to insulin resistance upon chronic exposure. PMID:25838073

The Glt1 glutamate receptor mediates the establishment and perpetuation of chronic visceral pain in an animal model of stress-induced bladder hyperalgesia.

PubMed

Ackerman, A Lenore; Jellison, Forrest C; Lee, Una J; Bradesi, Sylvie; Rodríguez, Larissa V

2016-04-01

Psychological stress exacerbates interstitial cystitis/bladder pain syndrome (IC/BPS), a lower urinary tract pain disorder characterized by increased urinary frequency and bladder pain. Glutamate (Glu) is the primary excitatory neurotransmitter modulating nociceptive networks. Glt1, an astrocytic transporter responsible for Glu clearance, is critical in pain signaling termination. We sought to examine the role of Glt1 in stress-induced bladder hyperalgesia and urinary frequency. In a model of stress-induced bladder hyperalgesia with high construct validity to human IC/BPS, female Wistar-Kyoto (WKY) rats were subjected to 10-day water avoidance stress (WAS). Referred hyperalgesia and tactile allodynia were assessed after WAS with von Frey filaments. After behavioral testing, we assessed Glt1 expression in the spinal cord by immunoblotting. We also examined the influence of dihydrokainate (DHK) and ceftriaxone (CTX), which downregulate and upregulate Glt1, respectively, on pain development. Rats exposed to WAS demonstrated increased voiding frequency, increased colonic motility, anxiety-like behaviors, and enhanced visceral hyperalgesia and tactile allodynia. This behavioral phenotype correlated with decreases in spinal Glt1 expression. Exogenous Glt1 downregulation by DHK resulted in hyperalgesia similar to that following WAS. Exogenous Glt1 upregulation via intraperitoneal CTX injection inhibited the development of and reversed preexisting pain and voiding dysfunction induced by WAS. Repeated psychological stress results in voiding dysfunction and hyperalgesia that correlate with altered central nervous system glutamate processing. Manipulation of Glu handling altered the allodynia developing after psychological stress, implicating Glu neurotransmission in the pathophysiology of bladder hyperalgesia in the WAS model of IC/BPS. Copyright © 2016 the American Physiological Society.

Antihypertensive Treatment Differentially Affects Vascular Sphingolipid Biology in Spontaneously Hypertensive Rats

PubMed Central

Spijkers, Léon J. A.; Janssen, Ben J. A.; Nelissen, Jelly; Meens, Merlijn J. P. M. T.; Wijesinghe, Dayanjan; Chalfant, Charles E.; De Mey, Jo G. R.; Alewijnse, Astrid E.; Peters, Stephan L. M.

2011-01-01

Background We have previously shown that essential hypertension in humans and spontaneously hypertensive rats (SHR), is associated with increased levels of ceramide and marked alterations in sphingolipid biology. Pharmacological elevation of ceramide in isolated carotid arteries of SHR leads to vasoconstriction via a calcium-independent phospholipase A2, cyclooxygenase-1 and thromboxane synthase-dependent release of thromboxane A2. This phenomenon is almost absent in vessels from normotensive Wistar Kyoto (WKY) rats. Here we investigated whether lowering of blood pressure can reverse elevated ceramide levels and reduce ceramide-mediated contractions in SHR. Methods and Findings For this purpose SHR were treated for 4 weeks with the angiotensin II type 1 receptor antagonist losartan or the vasodilator hydralazine. Both drugs decreased blood pressure equally (SBP untreated SHR: 191±7 mmHg, losartan: 125±5 mmHg and hydralazine: 113±14 mmHg). The blood pressure lowering was associated with a 20–25% reduction in vascular ceramide levels and improved endothelial function of isolated carotid arteries in both groups. Interestingly, losartan, but not hydralazine treatment, markedly reduced sphingomyelinase-induced contractions. While both drugs lowered cyclooxygenase-1 expression, only losartan and not hydralazine, reduced the endothelial expression of calcium-independent phospholipase A2. The latter finding may explain the effect of losartan treatment on sphingomyelinase-induced vascular contraction. Conclusion In summary, this study corroborates the importance of sphingolipid biology in blood pressure control and specifically shows that blood pressure lowering reduces vascular ceramide levels in SHR and that losartan treatment, but not blood pressure lowering per se, reduces ceramide-mediated arterial contractions. PMID:22195025

Stimulation of postsynapse adrenergic α2A receptor improves attention/cognition performance in an animal model of attention deficit hyperactivity disorder.

PubMed

Kawaura, Kazuaki; Karasawa, Jun-ichi; Chaki, Shigeyuki; Hikichi, Hirohiko

2014-08-15

A 5-trial inhibitory avoidance test using spontaneously hypertensive rat (SHR) pups has been used as an animal model of attention deficit hyperactivity disorder (ADHD). However, the roles of noradrenergic systems, which are involved in the pathophysiology of ADHD, have not been investigated in this model. In the present study, the effects of adrenergic α2 receptor stimulation, which has been an effective treatment for ADHD, on attention/cognition performance were investigated in this model. Moreover, neuronal mechanisms mediated through adrenergic α2 receptors were investigated. We evaluated the effects of both clonidine, a non-selective adrenergic α2 receptor agonist, and guanfacine, a selective adrenergic α2A receptor agonist, using a 5-trial inhibitory avoidance test with SHR pups. Juvenile SHR exhibited a shorter transfer latency, compared with juvenile Wistar Kyoto (WKY) rats. Both clonidine and guanfacine significantly prolonged the transfer latency of juvenile SHR. The effects of clonidine and guanfacine were significantly blocked by pretreatment with an adrenergic α2A receptor antagonist. In contrast, the effect of clonidine was not attenuated by pretreatment with an adrenergic α2B receptor antagonist, or an adrenergic α2C receptor antagonist, while it was attenuated by a non-selective adrenergic α2 receptor antagonist. Furthermore, the effects of neither clonidine nor guanfacine were blocked by pretreatment with a selective noradrenergic neurotoxin. These results suggest that the stimulation of the adrenergic α2A receptor improves the attention/cognition performance of juvenile SHR in the 5-trial inhibitory avoidance test and that postsynaptic, rather than presynaptic, adrenergic α2A receptor is involved in this effect. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of ACTH, dexamethasone, and adrenalectomy on 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the rat central nervous system

PubMed Central

Ye, Ping; Kenyon, Christopher J; MacKenzie, Scott M; Nichol, Katherine; Seckl, Jonathan R; Fraser, Robert; Connell, John M C; Davies, Eleanor

2008-01-01

Using a highly sensitive quantitative RT-PCR method for the measurement of CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) mRNAs, we previously demonstrated that CYP11B2 expression in the central nervous system (CNS) is subject to regulation by dietary sodium. We have now quantified the expression of these genes in the CNS of male Wistar Kyoto (WKY) rats in response to systemic ACTH infusion, dexamethasone infusion, and to adrenalectomy. CYP11B1 and CYP11B2 mRNA levels were measured in total RNA isolated from the adrenal gland and discrete brain regions using real-time quantitative RT-PCR. ACTH infusion (40 ng/day for 7 days, N=8) significantly increased CYP11B1 mRNA in the adrenal gland, hypothalamus, and cerebral cortex compared with animals infused with vehicle only. ACTH infusion decreased adrenal CYP11B2 expression but increased expression in all of the CNS regions except the cortex. Dexamethasone (10 μg/day for 7 days, N=8) reduced adrenal CYP11B1 mRNA compared with control animals but had no significant effect on either gene's expression in the CNS. Adrenalectomy (N=6 per group) significantly increased CYP11B1 expression in the hippocampus and hypothalamus and raised CYP11B2 expression in the cerebellum relative to sham-operated animals. This study confirms the transcription of CYP11B1 and CYP11B2 throughout the CNS and demonstrates that gene transcription is subject to differential regulation by ACTH and circulating corticosteroid levels. PMID:18252953

Inhaled ozone (O3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats.

PubMed

Miller, Desinia B; Karoly, Edward D; Jones, Jan C; Ward, William O; Vallanat, Beena D; Andrews, Debora L; Schladweiler, Mette C; Snow, Samantha J; Bass, Virginia L; Richards, Judy E; Ghio, Andrew J; Cascio, Wayne E; Ledbetter, Allen D; Kodavanti, Urmila P

2015-07-15

Air pollution has been linked to increased incidence of diabetes. Recently, we showed that ozone (O3) induces glucose intolerance, and increases serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that O3 exposure will cause systemic changes in metabolic homeostasis and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights. In the first experiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or O3 at 0.25, 0.50, or 1.0ppm, 6h/day for two days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0ppm O3, 6h/day for either one or two consecutive days, and systemic metabolic responses were determined immediately after or 18h post-exposure. O3 increased serum glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18h-post second exposure. O3 increased circulating metabolites of glycolysis, long-chain free fatty acids, branched-chain amino acids and cholesterol, while 1,5-anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycemic control, proteolysis and lipolysis. Liver gene expression increased for markers of glycolysis, TCA cycle and gluconeogenesis, and decreased for markers of steroid and fat biosynthesis. Genes involved in apoptosis and mitochondrial function were also impacted by O3. In conclusion, short-term O3 exposure induces global metabolic derangement involving glucose, lipid, and amino acid metabolism, typical of a stress-response. It remains to be examined if these alterations contribute to insulin resistance upon chronic exposure. Published by Elsevier Inc.

Regulation of natriuretic peptide receptor A and B expression by transforming growth factor-beta 1 in cultured aortic smooth muscle cells.

PubMed

Fujio, N; Gossard, F; Bayard, F; Tremblay, J

1994-06-01

Two types of natriuretic peptide receptors (NPR-A and NPR-B) are membrane guanylate cyclases whose relative expression varies in different tissues. Because natriuretic peptides have been shown to inhibit aortic smooth muscle proliferation, we investigated the regulation of NPR-A and NPR-B in these cells under different proliferative conditions. NPR subtype mRNA levels were measured by our newly developed quantitative reverse transcription-polymerase chain reaction assay using mutated NPR-A and NPR-B cRNA as internal standards. The functional impact of their expression was determined by atrial natriuretic peptide (ANP)- and C-type natriuretic peptide (CNP)-induced stimulation of cyclic GMP production. In the intact aorta, NPR-B mRNA levels were found to be 10-fold higher than those of NPR-A. This dominance was further amplified (1000-fold) in long-term cultures (10 to 15 passages) of aortic smooth muscle cells (ASMC). Higher cyclic GMP production with CNP than with ANP was observed in cultured ASMC from Wistar-Kyoto (WKY) rats. Similar stimulation by the two agonists was noted in spontaneously hypertensive rat (SHR) cells, paralleled by a 10-fold increase in NPR-A mRNA levels and ANP stimulation of cyclic GMP in hypertensive cells. The present study also evaluated NPR-A and NPR-B mRNA control by transforming growth factor-beta 1 (TGF-beta 1), an important regulator of cell proliferation that is overexpressed in SHR ASMC. TGF-beta 1 decreased both NPR-A and NPR-B mRNA levels with a predominant effect in SHR cells at high cell density.(ABSTRACT TRUNCATED AT 250 WORDS)

Test of Continental Drift by Comparison of Radiometric Ages: A pre-drift reconstruction shows matching geologic age provinces in West Africa and Northern Brazil.

PubMed

Hurley, P M; Rand, J R; Pinson, W H; Fairbairn, H W; de Almeida, F F; Melcher, G C; Cordani, U G; Kawashita, K; Vandoros, P

1967-08-04

1) The distribution of age values obtained by potassium-argon determinations and whole-rock rubidium-strontium determinations appears to be almost identical for West African rocks of the pervasive Eburnean Orogenic Cycle and basement rocks at opposite locations in South America. 2) There is also a close correlation, with respect to potassium-argon age determinations on micas, rubidium-strontium determinations on total-rock samples, and the extent to which these two sets of values differ, between rocks of the Pan-African Orogenic Cycle and rocks of the Caririan Orogenic Cycle in Brazil, where these two groups of rocks lie opposite each other in the two continents. 3) When Africa and South America are "fitted together," the sharply defined boundary between the Eburnean and the Pan-African age provinces in West Africa strikes directly toward the corresponding age boundary in northeast Brazil. 4) The transition from the 550-million-year Pan-African age province to the 2000-million-year age province in the Congo Craton in Cameroun-Gabon is matched in the rocks near the corresponding part of the east coast of Brazil. However the geological and age data are insufficient to do more than suggest the possibility of another age-boundary correlation here. 5) The evidence reported here supports the hypothesis of continental drift.

Comparative cardiopulmonary toxicity of exhausts from soy-based biofuels and diesel in healthy and hypertensive rats

PubMed Central

Bass, Virginia L.; Schladweiler, Mette C.; Nyska, Abraham; Thomas, Ronald F.; Miller, Desinia B.; Krantz, Todd; King, Charly; Gilmour, M. Ian; Ledbetter, Allen D.; Richards, Judy E.; Kodavanti, Urmila P.

2016-01-01

Increased use of renewable energy sources raise concerns about health effects of new emissions. We analyzed relative cardiopulmonary health effects of exhausts from (1) 100% soy biofuel (B100), (2) 20% soy biofuel + 80% low sulfur petroleum diesel (B20), and (3) 100% petroleum diesel (B0) in rats. Normotensive Wistar–Kyoto (WKY) and spontaneously hypertensive rats were exposed to these three exhausts at 0, 50, 150 and 500 μg/m3, 4 h/day for 2 days or 4 weeks (5 days/week). In addition, WKY rats were exposed for 1 day and responses were analyzed 0 h, 1 day or 4 days later for time-course assessment. Hematological parameters, in vitro platelet aggregation, bronchoalveolar lavage fluid (BALF) markers of pulmonary injury and inflammation, ex vivo aortic ring constriction, heart and aorta mRNA markers of vasoconstriction, thrombosis and atherogenesis were analyzed. The presence of pigmented macrophages in the lung alveoli was clearly evident with all three exhausts without apparent pathology. Overall, exposure to all three exhausts produced only modest effects in most endpoints analyzed in both strains. BALF γ-glutamyl transferase (GGT) activity was the most consistent marker and was increased in both strains, primarily with B0 (B0>B100>B20). This increase was associated with only modest increases in BALF neutrophils. Small and very acute increases occurred in aorta mRNA markers of vasoconstriction and thrombosis with B100 but not B0 in WKY rats. Our comparative evaluations show modest cardiovascular and pulmonary effects at low concentrations of all exhausts: B0 causing more pulmonary injury and B100 more acute vascular effects. BALF GGT activity could serve as a sensitive biomarker of inhaled pollutants. PMID:26514782

The educational settings of profoundly deaf children with cochlear implants compared with age-matched peers with hearing aids: implications for management.

PubMed

Archbold, Sue M; Nikolopoulos, Thomas P; Lutman, Mark E; O'Donoghue, Gerard M

2002-04-01

The educational settings of 42 implanted profoundly deaf children 3 years after implantation were compared with the respective settings of 635 age-matched severely deaf and 511 profoundly deaf children with hearing aids. All implanted children received their implants before beginning school. The results revealed that 3 years after implantation. 38% (16 children) of the implanted profoundly deaf children attended mainstream schools, whereas 57% (24 children) were in a unit, or special class, in a mainstream school, and 5% (two children) were in schools for the deaf. With regard to the age-matched profoundly deaf children with hearing aids, 12% (63 children) attended mainstream schools, whereas 55% (281 children) were in a unit of a mainstream school, and 33% (167 children) were in schools for the deaf. In the group of age-matched severely deaf children, 38% (239 children) attended mainstream schools, whereas 51% (326 children) were in a unit of a mainstream school, and 11% (70 children) were in schools for the deaf. Statistical analysis revealed a highly significant difference between the educational placement of implanted children and hearing-aided profoundly deaf children (p<0.00001), whereas there was no statistically significant difference between implanted children and hearing-aided severely deaf children. In conclusion, implanted profoundly deaf children who have received their implants before beginning school have the same profile of educational placement as aided severely deaf children rather than aided profoundly deaf children of the same age in the UK. This is likely to have significant implications for the future management of profoundly deaf children and to influence future planning of educational support services.

Age-related differences in enhancement and suppression of neural activity underlying selective attention in matched young and old adults.

PubMed

Haring, A E; Zhuravleva, T Y; Alperin, B R; Rentz, D M; Holcomb, P J; Daffner, K R

2013-03-07

Selective attention reflects the top-down control of sensory processing that is mediated by enhancement or inhibition of neural activity. ERPs were used to investigate age-related differences in neural activity in an experiment examining selective attention to color under Attend and Ignore conditions, as well as under a Neutral condition in which color was task-irrelevant. We sought to determine whether differences in neural activity between old and young adult subjects were due to differences in age rather than executive capacity. Old subjects were matched to two groups of young subjects on the basis of neuropsychological test performance: one using age-appropriate norms and the other using test scores not adjusted for age. We found that old and young subject groups did not differ in the overall modulation of selective attention between Attend and Ignore conditions, as indexed by the size of the anterior Selection Positivity. However, in contrast to either young adult group, old subjects did not exhibit reduced neural activity under the Ignore relative to Neutral condition, but showed enhanced activity under the Attend condition. The onset and peak of the Selection Positivity occurred later for old than young subjects. In summary, older adults execute selective attention less efficiently than matched younger subjects, with slowed processing and failed suppression under Ignore. Increased enhancement under Attend may serve as a compensatory mechanism. Copyright © 2013 Elsevier B.V. All rights reserved.

Sensorimotor Control of Tracking Movements at Various Speeds for Stroke Patients as Well as Age-Matched and Young Healthy Subjects

PubMed Central

Ao, Di; Song, Rong; Tong, Kai-yu

2015-01-01

There are aging- and stroke-induced changes on sensorimotor control in daily activities, but their mechanisms have not been well investigated. This study explored speed-, aging-, and stroke-induced changes on sensorimotor control. Eleven stroke patients (affected sides and unaffected sides) and 20 control subjects (10 young and 10 age-matched individuals) were enrolled to perform elbow tracking tasks using sinusoidal trajectories, which included 6 target speeds (15.7, 31.4, 47.1, 62.8, 78.5, and 94.2 deg/s). The actual elbow angle was recorded and displayed on a screen as visual feedback, and three indicators, the root mean square error (RMSE), normalized integrated jerk (NIJ) and integral of the power spectrum density of normalized speed (IPNS), were used to investigate the strategy of sensorimotor control. Both NIJ and IPNS had significant differences among the four groups (P<0.01), and the values were ranked in the following order: young controls < age-matched controls aging-induced increase in reliance on feedback control. The RMSE increased with the increase in the target speed and the NIJ and IPNS initially declined and then remained steady for all four groups, which indicated a shift from feedback to feedforward control as the target speed increased. The feedback-feedforward trade-off induced by stroke, aging and speed might be explained by a change in the transmission delay and neuromotor noise. The findings in this study improve our understanding of the mechanism underlying the sensorimotor control and neurological changes caused by stroke and aging. PMID:26030289

P300-based brain-computer interface (BCI) event-related potentials (ERPs): People with amyotrophic lateral sclerosis (ALS) vs. age-matched controls.

PubMed

McCane, Lynn M; Heckman, Susan M; McFarland, Dennis J; Townsend, George; Mak, Joseph N; Sellers, Eric W; Zeitlin, Debra; Tenteromano, Laura M; Wolpaw, Jonathan R; Vaughan, Theresa M

2015-11-01

Brain-computer interfaces (BCIs) aimed at restoring communication to people with severe neuromuscular disabilities often use event-related potentials (ERPs) in scalp-recorded EEG activity. Up to the present, most research and development in this area has been done in the laboratory with young healthy control subjects. In order to facilitate the development of BCI most useful to people with disabilities, the present study set out to: (1) determine whether people with amyotrophic lateral sclerosis (ALS) and healthy, age-matched volunteers (HVs) differ in the speed and accuracy of their ERP-based BCI use; (2) compare the ERP characteristics of these two groups; and (3) identify ERP-related factors that might enable improvement in BCI performance for people with disabilities. Sixteen EEG channels were recorded while people with ALS or healthy age-matched volunteers (HVs) used a P300-based BCI. The subjects with ALS had little or no remaining useful motor control (mean ALS Functional Rating Scale-Revised 9.4 (±9.5SD) (range 0-25)). Each subject attended to a target item as the items in a 6×6 visual matrix flashed. The BCI used a stepwise linear discriminant function (SWLDA) to determine the item the user wished to select (i.e., the target item). Offline analyses assessed the latencies, amplitudes, and locations of ERPs to the target and non-target items for people with ALS and age-matched control subjects. BCI accuracy and communication rate did not differ significantly between ALS users and HVs. Although ERP morphology was similar for the two groups, their target ERPs differed significantly in the location and amplitude of the late positivity (P300), the amplitude of the early negativity (N200), and the latency of the late negativity (LN). The differences in target ERP components between people with ALS and age-matched HVs are consistent with the growing recognition that ALS may affect cortical function. The development of BCIs for use by this population may begin

Capping the cost of compliance with the Kyoto Protocol and recycling revenues into land-use projects.

PubMed

Schlamadinger, B; Obersteiner, M; Michaelowa, A; Grubb, M; Azar, C; Yamagata, Y; Goldberg, D; Read, P; Kirschbaum, M U; Fearnside, P M; Sugiyama, T; Rametsteiner, E; Böswald, K

2001-07-14

There is the concern among some countries that compliance costs with commitments under the Kyoto Protocol may be unacceptably high. There is also the concern that technical difficulties with the inclusion of land use, land-use change, and forestry activities in non-Annex I countries might lead to an effective exclusion of such activities from consideration under the Protocol. This paper is proposing a mechanism that addresses both these concerns. In essence, it is suggested that parties should be able to purchase fixed-price offset certificates if they feel they cannot achieve compliance through other means alone, such as by improved energy efficiency, increased use of renewable energy, or use of the flexible mechanisms in the Kyoto Protocol. These offset certificates would act as a price cap for the cost of compliance for any party to the Protocol. Revenues from purchase of the offset certificates would be directed to forest-based activities in non-Annex I countries such as forest protection that may carry multiple benefits including enhancing net carbon sequestration.

Comparative peptidomic profile between human hypertrophic scar tissue and matched normal skin for identification of endogenous peptides involved in scar pathology.

PubMed

Li, Jingyun; Chen, Ling; Li, Qian; Cao, Jing; Gao, Yanli; Li, Jun

2018-08-01

Endogenous peptides recently attract increasing attention for their participation in various biological processes. Their roles in the pathogenesis of human hypertrophic scar remains poorly understood. In this study, we used liquid chromatography-tandem mass spectrometry to construct a comparative peptidomic profiling between human hypertrophic scar tissue and matched normal skin. A total of 179 peptides were significantly differentially expressed in human hypertrophic scar tissue, with 95 upregulated and 84 downregulated peptides between hypertrophic scar tissue and matched normal skin. Further bioinformatics analysis (Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis) indicated that precursor proteins of these differentially expressed peptides correlate with cellular process, biological regulation, cell part, binding and structural molecule activity ribosome, and PPAR signaling pathway occurring during pathological changes of hypertrophic scar. Based on prediction database, we found that 78 differentially expressed peptides shared homology with antimicrobial peptides and five matched known immunomodulatory peptides. In conclusion, our results show significantly altered expression profiles of peptides in human hypertrophic scar tissue. These peptides may participate in the etiology of hypertrophic scar and provide beneficial scheme for scar evaluation and treatments. © 2017 Wiley Periodicals, Inc.

Depression following fracture in women: a study of age-matched cohorts

PubMed Central

Williams, Lana J; Berk, Michael; Henry, Margaret J; Stuart, Amanda L; Brennan, Sharon L; Jacka, Felice N; Pasco, Julie A

2014-01-01

Objectives High levels of disability, functional impairment and mortality are independently associated with fracture and depression, however the relationship between fracture and depression is uncertain. The aim of this study was to investigate whether fracture is associated with subsequent depressive symptoms in a population-based sample of women. Design A study of age-matched fracture versus non-fracture cohorts of women. Setting Barwon Statistical Division, southeastern Australia. Participants Two samples of women aged ≥35 years were drawn from the Geelong Osteoporosis Study (GOS). The fracture cohort included women with incident fracture identified from radiology reports and the non-fracture cohort were randomly selected from the electoral roll during 1994–1996. Outcome measure Symptoms of depression for women with and without fracture during the 12-month period 2000–2001 were identified by self-report questionnaire based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Results A total of 296 women with fracture (12 hip, 48 vertebral, 91 wrist/forearm, 17 upper arm, 7 pelvis, 11 rib, 62 lower leg and 48 other fractures) and 590 women without fracture were included. Associations between fracture and depression differed between younger (≤65 years) and older (>65 years) women. Age and weight-adjusted odds ratio for depression following fracture among younger women was 0.62 (0.35 to 1.11, p=0.12) and 3.33 (1.24 to 8.98, p=0.02) for older women. Further adjustment for lifestyle factors did not affect the results. Conclusions This study demonstrated that differences in mood status exist between older and younger women following fracture and that fracture is associated with increased depression in older women. Assessment of mood status in both the short and long term following fracture in the elderly seems justified, with early detection and treatment likely to result in improved outcomes. PMID:24561497

Development of a national forest inventory for carbon accounting purposes in New Zealand's planted Kyoto forests

Treesearch

John Moore; Ian Payton; Larry Burrows; Chris Goulding; Peter Beets; Paul Lane; Peter Stephens

2007-01-01

This article discusses the development of a monitoring system to estimate carbon sequestration in New Zealand's planted Kyoto forests, those forests that have been planted since January 1, 1990, on land that previously did not contain forest. The system must meet the Intergovernmental Panel on Climate Change good practice guidance and must be seen to be unbiased,...

Time frequency power profile of QRS complex obtained with wavelet transform in spontaneously hypertensive rats.

PubMed

Takano, Nami K; Tsutsumi, Takeshi; Suzuki, Hiroshi; Okamoto, Yoshiwo; Nakajima, Toshiaki

2012-02-01

We evaluated whether frequency analysis could detect the development of interstitial fibrosis in rats. SHR/Izm and age-matched WKY/Izm were used. Limb lead II electrocardiograms were recorded. Continuous wavelet transform (CWT) was applied for the time-frequency analysis. The integrated time-frequency power (ITFP) between QRS complexes was measured and compared between groups. The ITFP at low-frequency bands (≤125Hz) was significantly higher in SHR/Izm. The percent change of ITFP showed the different patterns between groups. Prominent interstitial fibrosis with an increase in TIMP-1 mRNA expression was also observed in SHR/Izm. These results were partly reproduced in a computer simulation. Copyright © 2011 Elsevier Ltd. All rights reserved.

The general matching law describes choice on concurrent variable-interval schedules of wheel-running reinforcement.

PubMed

Belke, T W; Belliveau, J

2001-05-01

Six male Wistar rats were exposed to concurrent variable-interval schedules of wheel-running reinforcement. The reinforcer associated with each alternative was the opportunity to run for 15 s, and the duration of the changeover delay was 1 s. Results suggested that time allocation was more sensitive to relative reinforcement rate than was response allocation. For time allocation, the mean slopes and intercepts were 0.82 and 0.008, respectively. In contrast, for response allocation, mean slopes and intercepts were 0.60 and 0.03, respectively. Correction for low response rates and high rates of changing over, however, increased slopes for response allocation to about equal those for time allocation. The results of the present study suggest that the two-operant form of the matching law can be extended to wheel-running reinforcement. 'I'he effects of a low overall response rate, a short Changeover delay, and long postreinforcement pausing on the assessment of matching in the present study are discussed.

Comparison of polysomnographic data in age-, sex- and Axis I psychiatric diagnosis matched HIV-seropositive and HIV-seronegative insomnia patients.

PubMed

Low, Yinghui; Goforth, Harold W; Omonuwa, Toma; Preud'homme, Xavier; Edinger, Jack; Krystal, Andrew

2012-12-01

There is a high prevalence of insomnia in HIV-seropositive patients. Insomnia is associated with poorer disease outcomes, cognitive impairment and HIV-associated dementia. However there is limited data characterizing the type of sleep disturbances, and the cause. Previous studies report conflicting results, and observed changes in the distribution of REM and SWS were hypothesized to result from co-morbid mood disorders, although this is not established. We carried out this study to determine if there are differences in polysomnographic (PSG) sleep data in age-, sex- and Axis I diagnoses- matched HIV-seropositive and HIV-seronegative patients. Eighteen HIV-seropositive insomniacs were matched to HIV-seronegative insomniacs based on age, sex and Axis I diagnoses. Participants spent 2 consecutive nights in a sleep lab recording of PSG data. Multivariate analysis revealed an overall significant match-by-variable interaction (p=0.0126). Follow-up analysis show that compared to HIV-seronegative insomnia controls, HIV-seropositive insomniacs have significantly longer SOL, 8% decreased sleep efficiency, and 8-10% decreased time spent in REM sleep (p's<0.05). This study provides preliminary evidence that even after accounting for differences in age, sex and psychiatric diagnoses, HIV-seropositive patients with insomnia have significantly worse sleep than HIV-seronegative patients with insomnia. Unlike what previous authors have proposed, our results do not support the view that comorbid psychiatric disorders like depression are responsible for the observed differences in PSG findings and the greater incidence of insomnia, in HIV-seropositive patients when compared with other groups of insomnia patients. This suggests the presence of other etiologies including neuronal damage, psychosocial stressors, or comorbid medical conditions. Further studies are needed to determine the extent to which these play a role in insomnia in the HIV-seropositive population. Copyright © 2012

A method for age-matched OCT angiography deviation mapping in the assessment of disease- related changes to the radial peripapillary capillaries.

PubMed

Pinhas, Alexander; Linderman, Rachel; Mo, Shelley; Krawitz, Brian D; Geyman, Lawrence S; Carroll, Joseph; Rosen, Richard B; Chui, Toco Y

2018-01-01

To present a method for age-matched deviation mapping in the assessment of disease-related changes to the radial peripapillary capillaries (RPCs). We reviewed 4.5x4.5mm en face peripapillary OCT-A scans of 133 healthy control eyes (133 subjects, mean 41.5 yrs, range 11-82 yrs) and 4 eyes with distinct retinal pathologies, obtained using spectral-domain optical coherence tomography angiography. Statistical analysis was performed to evaluate the impact of age on RPC perfusion densities. RPC density group mean and standard deviation maps were generated for each decade of life. Deviation maps were created for the diseased eyes based on these maps. Large peripapillary vessel (LPV; noncapillary vessel) perfusion density was also studied for impact of age. Average healthy RPC density was 42.5±1.47%. ANOVA and pairwise Tukey-Kramer tests showed that RPC density in the ≥60yr group was significantly lower compared to RPC density in all younger decades of life (p<0.01). Average healthy LPV density was 21.5±3.07%. Linear regression models indicated that LPV density decreased with age, however ANOVA and pairwise Tukey-Kramer tests did not reach statistical significance. Deviation mapping enabled us to quantitatively and visually elucidate the significance of RPC density changes in disease. It is important to consider changes that occur with aging when analyzing RPC and LPV density changes in disease. RPC density, coupled with age-matched deviation mapping techniques, represents a potentially clinically useful method in detecting changes to peripapillary perfusion in disease.

Post-transplant outcomes of patients with and without hepatitis C virus infection according to donor age and gender matching.

PubMed

Grąt, Michał; Kornasiewicz, Oskar; Lewandowski, Zbigniew; Ligocka, Joanna; Grąt, Karolina; Wronka, Karolina Maria; Zieniewicz, Krzysztof; Krawczyk, Marek

2013-12-23

The purpose of this study was to evaluate the impact of donor age and donor-recipient gender matching on liver transplantation outcomes, focusing on differences between patients with and without hepatitis C virus (HCV) infection. This retrospective cohort study evaluated 622 liver transplantation recipients. HCV (n=164) and non-HCV (n=458) patients were subdivided by donor age (≤ 30, 31-50, and >50 years) and donor-recipient gender configurations. Five-year patient survival (PS) and graft survival (GS) were set as outcome measures. Five-year PS was 83.1% for HCV-positive and 81.6% for HCV-negative patients (p=0.614), with the corresponding GS rates of 81.2% and 79.3% (p=0.538), respectively. In HCV patients, transplantations from donors older than 50 years were associated with lower PS (p=0.035) and GS (p=0.006) than those from donors aged 31-50 years. This difference was not observed among non-HCV recipients (PS, p=0.994; GS, p=0.878). Regarding donor-recipient gender configurations, outcomes were similar in HCV (PS, p=0.751; GS, p=0.592) and non-HCV patients (PS, p=0.217; GS, p=0.249), except for a tendency toward lower PS for male-to-female transplantations than female-to-female transplantations in non-HCV patients (p=0.064). Outcomes of HCV patients were superior to those of non-HCV patients after transplantation from donors aged 31-50 years (PS, p=0.080; GS, p=0.026). Avoiding the transplantation of grafts from donors aged over 50 years to patients with HCV infection might improve the general outcomes of liver transplantation programs. There is no specific rationale for gender matching with respect to HCV status.

INHALED ENVIRONMENTAL COMBUSTION PARTICLES CAUISE MYOCARDIAL INJURY IN THE WISTAR KYOTO RAT

EPA Science Inventory

Abstract Epidemiologists have associated particulate matter (PM) air pollution with cardiovascular morbidity and premature mortality worldwide. However, direct experimental evidence showing causality and pathogenesis of PM-induced cardiovascular damage has been insufficient. We ...

Reference database of lung volumes and capacities in wistar rats from 2 to 24 months.

PubMed

Filho, Wilson Jacob; Fontinele, Renata Gabriel; de Souza, Romeu Rodrigues

2014-01-01

This study determines the effects of growing and aging on lung physiological volumes and capacities and the incidence of inflammation in the small airways with age in rats. A reference database comprising of body weight gain, lung physiological volumes and capacities and an anatomopathological study of lung lesions over 240 Wistar rats from two to 24 -mo, is described. Tidal volume (TV), minute respiratory volume (MRV), and forced vital capacity (FVC) decreased during the first six months of life and then remain constant until 24 -mo of age. The respiratory frequency (Rf) and dynamical compliance (Cdyn) maintain at constant values from 2 to 24- mo of age; the functional residual capacity (FRC) increases in the first 6 -mo and then remains constant up to 24 -mo. It was verified a less intensive inflammation in the small airways with age, when compared with the median and large airways. This study showed the normal parameters for lung volumes and capacities and the incidence of infections for growing and aging male and female rats. The age-related data on these main respiratory parameters in rats would be useful in studies of aging-related disorders using this model and for safety pharmacology studies necessary for the development of drugs.

The CD147/MMP-2 signaling pathway may regulate early stage cardiac remodelling in spontaneously hypertensive rats.

PubMed

Li, Bowei; Zhou, Wanxing; Yang, Xiaorong; Zhou, Yuliang; Tan, Yongjing; Yuan, Congcong; Song, Yulan; Chen, Xiao; Zhang, Wei

2016-11-01

Previous studies have reported that decreased matrix metalloproteinase-2 (MMP-2) is associated with early stage (age 8-16 weeks) ventricular remodelling in spontaneously hypertensive rats (SHR). We hypothesized that inhibited CD147/MMP-2 signalling might down-regulate MMP-2 expression and augment remodelling in spontaneously hypertensive rats. Twenty-nine male SHR (8 weeks) were randomly assigned to SHR, CD147, and CD147+DOX groups. The control group included eight age-matched WKY rats. CD147 and CD147+DOX groups received recombinant human CD147 (600 ng/kg in 1.5 mL saline, weekly). The SHR and WKY groups received the vehicle. The CD147+DOX group also received doxycycline, an inhibitor of MMPs (daily, 30 mg/kg in 1.5 mL saline, iG). On day 56 echocardiography and left ventricular mass index (LVWI) measurements were collected and histological sections were stained for cell and collagen content. Myocardium MMP-2, TIMP-1, CD147, and collagens types I and III were estimated by western blot. CD147 and the ratio of MMP-2/TIMP-1 were lower in SHR than WKY rats (P<.05). Myocyte hypertrophy, partial fibre breaks, plasmolysis, necrosis and collagen content (collagen volume fraction [CVF], I and III) in SHR were above control levels (P<.05). CD147 rats showed CD147, MMP-2 and MMP-2/TIMP-1 were increased (P<.05), CVF, LVWI, and collagen I and III were decreased (P<.05) and myocyte morphology was improved. CD147 levels did not differ between CD147+DOX and CD147 groups, CVF, collagens type I and III and partial fiber breaks were more abundant in CD147+DOX (P<.05). In summary, an inhibited CD147/MMP-2 pathway was associated with early stage cardiac remodelling, and CD147 supplementation may attenuate this response. © 2016 John Wiley & Sons Australia, Ltd.

Rapamycin suppresses brain aging in senescence-accelerated OXYS rats

PubMed Central

Kolosova, Nataliya G.; Vitovtov, Anton O.; Muraleva, Natalia A; Akulov, Andrey E.; Stefanova, Natalia A.; Blagosklonny, Mikhail V.

2013-01-01

Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span in C elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wistar rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging. PMID:23817674

Predictors of Premature Match Closure in Youth Mentoring Relationships.

PubMed

Kupersmidt, Janis B; Stump, Kathryn N; Stelter, Rebecca L; Rhodes, Jean E

2017-03-01

Although mentoring is a popular and effective means of intervention with youth, the positive effects of mentoring can be diminished by premature match closure of relationships. Program, mentor, and mentee characteristics were examined as predictors of premature match closure. Secondary data analyses were conducted on a large national database of mentoring programs consisting of match and youth risk information from 170 mentoring programs and 6468 matches from across the U.S. Premature closure was associated with mentee age at match inception and 19 individual mentee characteristics. The set of mentee characteristics were examined as part of a cumulative risk index encompassing seven conceptually combined categories including family background characteristics, school functioning problems, engagement in risky health behaviors, self-regulation difficulties, engagement in illegal or criminal activities, and internalizing and externalizing behavior problems. Both the age of mentees when matched and the cumulative risk index score significantly predicted premature closure. Results are discussed in terms of directions for future research and suggestions for enhancing mentoring program practices. © Society for Community Research and Action 2017.

The retinal nerve fibre layer thickness in glaucomatous hydrophthalmic eyes assessed by scanning laser polarimetry with variable corneal compensation in comparison with age-matched healthy children.

PubMed

Hložánek, Martin; Ošmera, Jakub; Ležatková, Pavlína; Sedláčková, Petra; Filouš, Aleš

2012-12-01

To compare the thickness of the retinal nerve fibre layer (RNFL) in hydrophthalmic glaucomatous eyes in children with age-matched healthy controls using scanning laser polarimetry with variable corneal compensation (GDxVCC). Twenty hydrophthalmic eyes of 20 patients with the mean age of 10.64 ± 3.02 years being treated for congenital or infantile glaucoma were included in the analysis. Evaluation of RNFL thickness measured by GDxVCC in standard Temporal-Superior-Nasal-Inferior-Temporal (TSNIT) parameters was performed. The results were compared to TSNIT values of an age-matched control group of 120 healthy children published recently as referential values. The correlation between horizontal corneal diameter and RNFL thickness in hydrophthalmic eyes was also investigated. The mean ± SD values in TSNIT Average, Superior Average, Inferior Average and TSNIT SD in hydrophthalmic eyes were 52.3 ± 11.4, 59.7 ± 17.1, 62.0 ± 15.6 and 20.0 ± 7.8 μm, respectively. All these values were significantly lower compared to referential TSNIT parameters of age-matched healthy eyes (p = 0.021, p = 0.001, p = 0.003 and p = 0.018, respectively). A substantial number of hydrophthalmic eyes laid below the level of 5% probability of normality in respective TSNIT parameters: 30% of the eyes in TSNIT average, 50% of the eyes in superior average, 30% of the eyes in inferior average and 45% of the eyes in TSNIT SD. No significant correlation between enlarged corneal diameter and RNFL thickness was found. The mean values of all standard TSNIT parameters assessed using GDxVCC in hydrophthalmic glaucomatous eyes in children were significantly lower in comparison with referential values of healthy age-matched children. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

Cyclists Have Greater Chondromalacia Index Than Age-Matched Controls at the Time of Hip Arthroscopy.

PubMed

Stone, Austin V; Howse, Elizabeth A; Mannava, Sandeep; Stubbs, Allston J

2016-10-01

To evaluate the clinical symptoms and intraoperative pathology associated with hip pain in the cyclist compared with a matched hip arthroscopy surgical group. In an institutional review board-approved study, we retrospectively reviewed a prospective database of 1,200 consecutive hip arthroscopy patients from 2008 to 2015. Adult patients were identified who reported cycling as a major component of their activity. Patients were age, gender, and body mass index matched to a control, noncycling group. Pain symptoms, preoperative examinations, radiographic and operative findings were compared. Primary outcome variables included the femoral and acetabular Outerbridge chondromalacia grade. Additional outcome measurements included the involved area and the chondromalacia index (CMI; the product of the Outerbridge chondromalacia grade and surface area [mm 2  × severity]). A total of 167 noncyclists were matched to the cycling group (n = 16). Cyclists had significantly greater femoral head chondromalacia grade (2.0 [95% confidence interval (CI), 1.5-2.5] v 1.4 [95% CI, 1.3-1.6], P = .043), femoral head chondromalacia area (242 mm 2 [95% CI, 191-293 mm 2 ] v 128 mm 2 [95% CI, 113-141 mm 2 ], P < .001), and femoral head CMI (486 [95% CI, 358-615] v 247 [95% CI, 208-286], P = .001) assessed intraoperatively. Hip pain in cyclists positively correlated with an increased acetabular center-edge angle (R = 0.261, P < .001) and an increased Tonnis grade (R = 0.305, P < .001). Cyclists were also more likely to have a coxalgic gait on physical examination (R = 0.250, P = .006). Cyclists had a greater degree of femoral chondromalacia than a matched group of noncyclists. Cycling activity positively correlated with the presence of femoral chondromalacia with clinically significant gait alterations. These data support the hypothesis that cyclists with hip pain have more chondral pathology than a similar group of other patients with hip pain. Ultimately, cyclists with hip pain

A dynamic model of the marriage market-part 1: matching algorithm based on age preference and availability.

PubMed

Matthews, A P; Garenne, M L

2013-09-01

The matching algorithm in a dynamic marriage market model is described in this first of two companion papers. Iterative Proportional Fitting is used to find a marriage function (an age distribution of new marriages for both sexes), in a stable reference population, that is consistent with the one-sex age distributions of new marriages, and includes age preference. The one-sex age distributions (which are the marginals of the two-sex distribution) are based on the Picrate model, and age preference on a normal distribution, both of which may be adjusted by choice of parameter values. For a population that is perturbed from the reference state, the total number of new marriages is found as the harmonic mean of target totals for men and women obtained by applying reference population marriage rates to the perturbed population. The marriage function uses the age preference function, assumed to be the same for the reference and the perturbed populations, to distribute the total number of new marriages. The marriage function also has an availability factor that varies as the population changes with time, where availability depends on the supply of unmarried men and women. To simplify exposition, only first marriage is treated, and the algorithm is illustrated by application to Zambia. In the second paper, remarriage and dissolution are included. Copyright © 2013 Elsevier Inc. All rights reserved.

A demographic and social profile of age- and sex-matched vegetarians and nonvegetarians.

PubMed

Freeland-Graves, J H; Greninger, S A; Young, R K

1986-07-01

A demographic and social profile was compiled for 150 vegetarians and 150 nonvegetarians who were matched for age and sex. A 328-item questionnaire containing both closed- and open-ended questions was administered. Information collected included personal and demographic data, personal habits, social activities, and possible influences of vegetarianism. No differences were observed in the cultural, ethnic, or familial background of the groups. Vegetarians were less influenced by parents and traditional religions, were slightly less well educated, and were employed in less-skilled occupations. However, vegetarians socialized more than nonvegetarians, as evidenced by their greater frequency of entertaining, going out with friends, and joining organizations. The commitment to vegetarianism was strong and appeared to be reinforced by an extensive network of family and friends who were also vegetarians. This strong support network was particularly evident for those who practiced the more restrictive forms of vegetarianism, the only major difference observed within the types of vegetarians studied.

Prosody Perception and Production in Children with Hearing Loss and Age- and Gender-Matched Controls.

PubMed

Kalathottukaren, Rose Thomas; Purdy, Suzanne C; Ballard, Elaine

2017-04-01

Auditory development in children with hearing loss, including the perception of prosody, depends on having adequate input from cochlear implants and/or hearing aids. Lack of adequate auditory stimulation can lead to delayed speech and language development. Nevertheless, prosody perception and production in people with hearing loss have received less attention than other aspects of language. The perception of auditory information conveyed through prosody using variations in the pitch, amplitude, and duration of speech is not usually evaluated clinically. This study (1) compared prosody perception and production abilities in children with hearing loss and children with normal hearing; and (2) investigated the effect of age, hearing level, and musicality on prosody perception. Participants were 16 children with hearing loss and 16 typically developing controls matched for age and gender. Fifteen of the children with hearing loss were tested while using amplification (n = 9 hearing aids, n = 6 cochlear implants). Six receptive subtests of the Profiling Elements of Prosody in Speech-Communication (PEPS-C), the Child Paralanguage subtest of Diagnostic Analysis of Nonverbal Accuracy 2 (DANVA 2), and Contour and Interval subtests of the Montreal Battery of Evaluation of Amusia (MBEA) were used. Audio recordings of the children's reading samples were rated using a perceptual prosody rating scale by nine experienced listeners who were blinded to the children's hearing status. Thirty two children, 16 with hearing loss (mean age = 8.71 yr) and 16 age- and gender-matched typically developing children with normal hearing (mean age = 8.87 yr). Assessments were completed in one session lasting 1-2 hours in a quiet room. Test items were presented using a laptop computer through loudspeaker at a comfortable listening level. For children with hearing loss using hearing instruments, all tests were completed with hearing devices set at their everyday listening setting. All PEPS

Anaerobic digestion of organic waste in Japan: the first demonstration plant at Kyoto City.

PubMed

Komatsu, T; Kimura, T; Kuriyama, Y; Isshiki, Y; Kawano, T; Hirao, T; Masuda, M; Yokoyama, K; Matsumoto, T; Takeda, M

2002-01-01

Recycling of Municipal Solid Waste is vigorously promoted in Japan and the necessity of energy recovery from organic waste is increasing. An anaerobic digestion demonstration plant for organic waste in Kyoto City, Japan has been operated for about two years. Three kinds of wastes (garbage and leftovers from hotels, yard waste and used paper) mixed at various ratios are used. The plant has maintained stable operations with each mixture, generating biogas by the decomposition of VS at the rate of about 820 m3N/ton-VS.

Osseointegration of alumina bioceramic granules: A comparative experimental study

NASA Astrophysics Data System (ADS)

Rerikh, V. V.; Avetisyan, A. R.; Zaydman, A. M.; Anikin, K. A.; Bataev, V. A.; Nikulina, A. A.; Sadovoy, M. A.; Aronov, A. M.; Semantsova, E. S.

2016-08-01

To perform a comparative analysis of osseointegration of bioceramic alumina-based granules, hydroxyapatite-based granules, and deproteinized bone granules. The experiment was conducted on 52 adult male Kyoto-Wistar rats weighing 350 to 520 g. The animals were divided into five matched groups that differed only in the type of an implanted material. The granules were implanted in the lumbar vertebral bodies and in the distal right femur of each laboratory animal. Two months after surgery, the animals were euthanized, followed by tissue sampling for morphological studies. An examination of specimens from the groups with implanted alumina granules revealed the newly formed trabecular bone with remodeling signs. The bone tissue filled the intragranular space, tightly adhering to the granule surface. There was no connective tissue capsule on the border between bone tissue and alumina granules. Cylindrical bioceramic alumina-based granules with an open internal channel have a higher strength surpassing than that of analogs and the osseointegration ability close to that of hydroxyapatite and deproteinized bone granules.

Suppression of endoplasmic reticulum stress improves endothelium-dependent contractile responses in aorta of the spontaneously hypertensive rat

PubMed Central

Matsumoto, Takayuki; Webb, R. Clinton

2013-01-01

A contributing factor to increased peripheral resistance seen during hypertension is an increased production of endothelium-derived contractile factors (EDCFs). The main EDCFs are vasoconstrictor prostanoids, metabolites of arachidonic acid (AA) produced by Ca2+-dependent cytosolic phospholipase A2 (cPLA2) following phosphorylation (at Ser505) mediated by extracellular signal-regulated kinase (ERK1/2) and cyclooxygenase (COX) activations. Although endoplasmic reticulum (ER) stress has been shown to contribute to pathophysiological alterations in cardiovascular diseases, the relationship between ER stress and EDCF-mediated responses remains unclear. We tested the hypothesis that ER stress plays a role in EDCF-mediated responses via activation of the cPLA2/COX pathway in the aorta of the spontaneously hypertensive rat (SHR). Male SHR and Wistar-Kyoto rats (WKY) were treated with ER stress inhibitor, tauroursodeoxycholic acid or 4-phenlybutyric acid (TUDCA or PBA, respectively, 100 mg·kg−1·day−1 ip) or PBS (control, 300 μl/day ip) for 1 wk. There was a decrease in systolic blood pressure in SHR treated with TUDCA or PBA compared with control SHR (176 ± 3 or 181 ± 5, respectively vs. 200 ± 2 mmHg). In the SHR, treatment with TUDCA or PBA normalized aortic (vs. control SHR) 1) contractions to acetylcholine (ACh), AA, and tert-butyl hydroperoxide, 2) ACh-stimulated releases of prostanoids (thromboxane A2, PGF2α, and prostacyclin), 3) expression of COX-1, 4) phosphorylation of cPLA2 and ERK1/2, and 5) production of H2O2. Our findings demonstrate a novel interplay between ER stress and EDCF-mediated responses in the aorta of the SHR. Moreover, ER stress inhibition normalizes such responses by suppressing the cPLA2/COX pathway. PMID:23709602

A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance.

PubMed

Bosse, John D; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E Dale; Pereira, Troy J; Dolinsky, Vernon W; Symons, J David; Jalili, Thunder

2013-06-15

Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-HF had lower (P < 0.05) mean arterial pressure than SHR-C (148 ± 3 vs. 159 ± 3 mmHg) but a similar degree of cardiac hypertrophy (33.4 ± 0.4 vs. 33.1 ± 0.4 heart weight/tibia length, mg/mm). Mesenteric arteries and the entire aorta were used to assess vascular function and endothelial nitric oxide synthase (eNOS) signaling, respectively. Endothelium-dependent (acetylcholine) relaxation of mesenteric arteries was improved (P < 0.05) in SHR-HF vs. SHR-C, whereas contraction (potassium chloride, phenylephrine) was reduced (P < 0.05). Phosphorylation of eNOSSer1177 increased (P < 0.05) in arteries from SHR-HF vs. SHR-C. Plasma glucose, insulin, and homoeostatic model of insulin assessment were lower (P < 0.05) in SHR-HF vs. SHR-C, whereas peripheral insulin sensitivity (insulin tolerance test) was similar. After a 10-h fast, insulin stimulation (2 U/kg ip) increased (P < 0.05) phosphorylation of AktSer473 and S6 in heart and gastrocnemius similarly in SHR-C vs. SHR-HF. In conclusion, a low-carbohydrate/high-fat diet reduced blood pressure and improved arterial function in SHR without producing signs of insulin resistance or altering insulin-mediated signaling in the heart, skeletal muscle, or vasculature.

A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance

PubMed Central

Bosse, John D.; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E. Dale; Pereira, Troy J.; Dolinsky, Vernon W.; Symons, J. David

2013-01-01

Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-HF had lower (P < 0.05) mean arterial pressure than SHR-C (148 ± 3 vs. 159 ± 3 mmHg) but a similar degree of cardiac hypertrophy (33.4 ± 0.4 vs. 33.1 ± 0.4 heart weight/tibia length, mg/mm). Mesenteric arteries and the entire aorta were used to assess vascular function and endothelial nitric oxide synthase (eNOS) signaling, respectively. Endothelium-dependent (acetylcholine) relaxation of mesenteric arteries was improved (P < 0.05) in SHR-HF vs. SHR-C, whereas contraction (potassium chloride, phenylephrine) was reduced (P < 0.05). Phosphorylation of eNOSSer1177 increased (P < 0.05) in arteries from SHR-HF vs. SHR-C. Plasma glucose, insulin, and homoeostatic model of insulin assessment were lower (P < 0.05) in SHR-HF vs. SHR-C, whereas peripheral insulin sensitivity (insulin tolerance test) was similar. After a 10-h fast, insulin stimulation (2 U/kg ip) increased (P < 0.05) phosphorylation of AktSer473 and S6 in heart and gastrocnemius similarly in SHR-C vs. SHR-HF. In conclusion, a low-carbohydrate/high-fat diet reduced blood pressure and improved arterial function in SHR without producing signs of insulin resistance or altering insulin-mediated signaling in the heart, skeletal muscle, or vasculature. PMID:23604708

Cyanidin 3-O-glucoside prevents the development of maladaptive cardiac hypertrophy and diastolic heart dysfunction in 20-week-old spontaneously hypertensive rats.

PubMed

Aloud, Basma Milad; Raj, Pema; McCallum, Jason; Kirby, Chris; Louis, Xavier Lieben; Jahan, Fahmida; Yu, Liping; Hiebert, Brett; Duhamel, Todd A; Wigle, Jeffrey T; Blewett, Heather; Netticadan, Thomas

2018-06-20

The present study investigated the effects of cyanidin 3-O-glucoside (C3G) in cardiomyocytes (CM) and fibroblasts exposed to endothelin 1 (ET1), as well as in the spontaneously hypertensive rat (SHR) model, alone or in combination with hydrochlorothiazide (HCT). Adult rat CM and cardiac fibroblasts (CF) were pretreated with C3G and co-incubated with ET1 (10-7 M) for 24 hours. Five-week-old male SHR and their normotensive controls, Wistar-Kyoto rats (WKY), received one of 4 treatments via oral gavage daily for 15 weeks: (1) water (control); (2) C3G (10 mg per kg per day); (3) HCT (10 mg per kg per day); (4) C3G + HCT (10 mg per kg per day each). Blood pressure (BP) was measured at 1, 8 and 15 weeks. Echocardiography measurements were performed at 15 weeks. C3G prevented ET1-induced CM death and hypertrophy. Stimulating CF with ET1 did not induce their phenoconversion; nevertheless, C3G inhibited un-stimulated CF differentiation. HCT slowed the rise of systolic BP (SBP) in the SHR over time (week 1: SHRs control = 161 ± 6.3 mmHg, SHRs HCT = 129 ± 6.3 mmHg; week 15: SHRs control = 201 ± 7.3 mmHg, SHRs HCT = 168 ± 7.3 mmHg), but C3G had no effect on SBP (week 1: SHRs control = 161 ± 6.3 mmHg, SHRs C3G = 126 ± 6.3 mmHg; week 15: SHRs control = 201 ± 7.3 mmHg, SHRs C3G = 186 ± 7.3 mmHg). SHRs treated with C3G, HCT, and C3G + HCT had lower left ventricular mass and shorter isovolumetric relaxation time compared to control SHRs. C3G ameliorated cardiac hypertrophy and diastolic dysfunction in SHRs.

In vitro vascular effects produced by crude aqueous extract of green marine algae, Cladophora patentiramea (Mont.) Kützing, in aorta from normotensive rats.

PubMed

Lim, Yee-Ling; Mok, Shiueh-Lian

2010-01-01

To investigate the antihypertensive activity of aqueous extracts obtained from Malaysian coastal seaweeds and to determine the pharmacological mechanisms of the extracts on rat aorta in vitro. The antihypertensive activity of 11 species of seaweeds (5 brown, 1 red and 5 green algae) were tested by cumulative addition of the extracts to phenylephrine (PE)-precontracted Wistar-Kyoto (WKY) aortic rings in in vitro isometric contraction studies. Mechanisms for vasorelaxant effect were investigated in the presence of various antagonists. Of the 11 species tested, 2 showed a vasorelaxant effect. Further investigation of the mechanisms of action of the aqueous extract of green alga, Cladophora patentiramea (AECP),showed that the vascular relaxant effect was endothelium- and concentration-dependent. A maximum relaxation of 45.8 +/- 4.6% (n = 8, p < 0.001) was obtained at 0.1 mg/ml of extract, after which the response was found to reduce in a concentration-dependent manner to 15.7 +/- 4.9% (n = 8, p < 0.001) at the highest extract concentration tested. Pretreatment of endothelium-intact aortic rings with Nomega-nitro-L-arginine methyl ester (L-NAME, 30 microM), (1)H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM) and methylene blue (100 microM) resulted in a complete blockade of AECP-induced vasorelaxation. However, the relaxant effects of the extract were not blocked by atropine (1 microM), indomethacin (10 microM) and glibenclamide (10 microM), although the maximum relaxant responses were enhanced in the presence of glibenclamide. Our data showed that the in vitro vascular relaxant effect of AECPwas mediated through endothelium-dependent nitric oxide-cGMP pathway, and was not associated with the release of vasodilator prostaglandins, activation of muscarinic receptors, or ATP-sensitive potassium channels opening. Copyright 2010 S. Karger AG, Basel.

Increased vascular sensitivity and connexin43 expression after sympathetic denervation.

PubMed

Slovut, David P; Mehta, Shyamal H; Dorrance, Anne M; Brosius, Frank C; Watts, Stephanie W; Webb, R Clinton

2004-05-01

Following denervation, arteries demonstrate a heightened sensitivity to alpha-adrenergic agonists and increased oscillatory contractions that may partly result from increased gap junction expression. Hence, we wanted to study the effect of sympathetic denervation on connexin43 (Cx43) expression and agonist-induced contractility in the vascular smooth muscle (VSM). Effects of denervation with reserpine (3 mg/kg/day, i.p.) or topical 5% phenol-glycerol on VSM contractions and expression of the gap junction Cx43 mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting for Cx43 protein were examined. Wistar-Kyoto (WKY) rat tail arteries were exposed to norepinephrine (NE) (10(-9)-10(-5) M). Reactivity was also examined in the carotid arteries and thoracic aortas from Cx43 heterozygote deficient (KO) mice. The concentration for NE-induced contraction was lower in reserpine- and phenol-treated vessels than controls (p<0.05). NE-induced oscillatory activity (OA) was seen in 5/5 reserpine- and 5/8 phenol-treated vessels vs. 0/12 controls (p<0.05). Spontaneous OA was observed more frequently in carotid and aortic rings from WT than Cx43 KO rings. Cumulative OA in response to alpha-adrenergic stimulation was significantly greater in WT carotid (429+/-101 vs. 128+/-7 mN s, p<0.05) and aortic rings (337+/-85 vs. 134+/-11 mN s, p<0.05) than in Cx43 KO rings. Following denervation, RT-PCR showed significantly increased levels of Cx43 mRNA (p<0.05). Western blot analysis revealed near doubling of Cx43 protein (p<0.05). We conclude that sympathetic denervation results in increased expression of Cx43, which in turn, contributes to increased spontaneous and agonist-induced OA in VSM.

Effects of cadmium on the renal and skeletal muscle microcirculation in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Chong.

1990-01-01

The effects of cadmium on the arteriolar diameters of the kidney and skeletal muscle were quantified, because of the hypertensive effect of cacmium. The effect of cacmium on the constrictor response of the renal arterioles to angiotensin II (Ang II) were also assessed. In vivo preparations of the rat hydronephrotic kidney and cremaster muscle were used for direct visualization of the microvessels with intravital television microscopy. Hydronephrosis was induced in twenty-seven male Wistar-Kyoto rats (150-180 g) by unilateral ureter ligation. The hydronephrotic kidney, with intact cortical circulation and innervation, was exteriorized in a specially designed bath for microcirculation observation 6-8more » weeks following the ureter ligation. The cremaster muscle experiments were conducted in another thirty-seven male WKY rats (120-180 g). Disparate effects of cadmium were observed in these two microcirculation beds. Topical cadmium (1.35 [mu]M-0.45 mM) increased the diameters of the pre- and postglomerular vessels in the hydronephrotic kidney maximally by 15-26%. Cadmium (0.27 mM) inhibited the Ang II response of the arterioles non-competitively. However, intraperitoneally injected cadmium (2 mg/kg), which significantly increased the mean arterial pressure, did not dilate the arterioles nor alter the Ang II response. On the other hand, cadmium (13.5 [mu]M-0.72 mM) constricted the larger arterioles in the cremaster muscle (60-160 [mu]m) concentration-dependently, but not small arterioles (15-30 [mu]m). In summary, topical cadmium dilates renal arterioles and decreases their reactivity to Ang II, but constricts the larger cremaster arterioles. The disparate effects of cadmium suggest different Ca[sup 2+] utilization mechanisms in different vascular beds. The construction of the cremaster arterioles may contribute to cadmium-induced hypertension by increasing peripheral resistance.« less

Age-Related Normogram for Ovarian Antral Follicle Count in Women with Polycystic Ovary Syndrome and Comparison with Age Matched Controls Using Magnetic Resonance Imaging.

PubMed

Aiyappan, Senthil Kumar; Karpagam, Bulabai; Vadanika, V; Chidambaram, Prem Kumar; Vinayagam, S; Saravanan, K C

2016-01-01

Antral Follicle count (AFC) is a reliable marker for ovarian reserve. Previous studies have used transvaginal ultrasound for estimation of AFC, however we used magnetic resonance imaging (MRI) for estimation of AFC and for creating an age-related normogram in patients with polycystic ovary syndrome (PCOS) and compared it with normal patients. The aim of this study is to create an age related normogram for AFC in women with PCOS and to compare that with women without polycystic ovarian syndrome using MRI. A total of 1500 women were examined, out of which 400 fitted the criteria for PCOS. They all underwent MRI study and similar age matched women without PCOS also underwent MRI examination. Normogram for AFC were obtained using LMS software and a percentile chart was obtained. Normogram for AFC in PCOS women showed decline in number of AFC as the age progresses and the decline was linear. The normogram for AFC was compared with equal number of patients without PCOS and they also showed decline in AFC as the age progresses, however the decline was exponential and faster. Age related normogram for AFC is widely used and considered as best clinical predictor for ovarian response in assisted reproductive technology. Knowledge of ovarian reserve is important in PCOS and non-PCOS females as PCOS patients are at risk for ovarian hyperstimulation syndrome during gonadotrophin theraphy. MRI is an equally effective and in some times better alternative to transvaginal ultrasound as it has got its own advantages.

Kinematic Movement Strategies in Primary School Children with 22q11.2 Deletion Syndrome Compared to Age- and IQ-Matched Controls during Visuo-Manual Tracking

ERIC Educational Resources Information Center

Van Aken, Katrijn; Swillen, Ann; Beirinckx, Marc; Janssens, Luc; Caeyenberghs, Karen; Smits-Engelsman, Bouwien

2010-01-01

The present study focused on the mechanism subserving the production of kinematic patterns in 21 children with 22q11.2DS (mean age=9.6 [plus or minus] 1.9; mean FSIQ=73.05 [plus or minus] 10.2) and 21 age- and IQ-matched control children (mean age=9.6 [plus or minus] 1.9; mean FSIQ=73.38 [plus or minus] 12.0) when performing a visuo-manual…

Individualized behavioral assessments and maternal ratings of mastery motivation in mental age-matched toddlers with and without motor delay.

PubMed

Wang, Pei-Jung; Morgan, George A; Hwang, Ai-Wen; Liao, Hua-Fang

2013-01-01

Mastery motivation is a precursor of future developmental outcomes. Evidence about whether toddlers with motor delay have lower mastery motivation is inconclusive. The purpose of this study was to examine differences between mental age-matched toddlers with and without motor delay on various mastery motivation indicators. A mental age- and sex-matched case-control study was performed. Twenty-two children with motor delay, aged 23 to 47 months, and 22 children who were developing typically, aged 15 to 29 months, were recruited. Persistence and mastery pleasure were measured with behavioral tasks that were moderately challenging for each child and with maternal ratings using the Dimensions of Mastery Questionnaire (DMQ). The DMQ was rated by each child's mother based on her perception of her child's motivation. Two types of structured tasks (a puzzle and a cause-effect toy selected to be moderately challenging for each child) were administered in a laboratory setting and recorded on videos. Paired t tests or Wilcoxon signed rank tests were used to examine group differences in persistence and mastery pleasure (α=.007, 2-tailed). Children with motor delay were rated lower on DMQ persistence than the typically developing group, but they did not show significantly lower persistence on the structured tasks. There were no significant differences in mastery pleasure between the 2 groups on either measure. Large within-sample variability on the tasks and small sample size makes subgroup analysis (eg, different severities) difficult. Toddlers with motor delay did not show lower persistence and pleasure when given tasks that were moderately challenging; however, their mothers tended to view them as having lower motivation. Clinicians and parents should provide appropriately challenging tasks to increase children's success and motivation.

Topographic Distribution of the Sand Flea Tunga penetrans in Wistar Rats and Humans in Two Endemic Areas in Brazil

PubMed Central

Buckendahl, John; Heukelbach, Jörg; Witt, Lars; Schwalfenberg, Stefan; Calheiros, Cláudia M. L.; Feldmeier, Hermann

2012-01-01

Tungiasis is a zoonosis caused by Tunga penetrans. In Brazil, tungiasis is endemic in many resource-poor communities, in which various domestic and sylvatic animals act as reservoirs. Eighty laboratory-raised Wistar rats were exposed to T. penetrans in areas of intense transmission: a fishing village and an urban shantytown in Ceará State, northeast Brazil. The topographic distribution of lesions in Wistar rats was compared with the distribution of lesions in humans in the same area. Our results show that the topographic distribution of embedded sand fleas was almost identical in Wistar rats and humans and that lesions were confined to the feet. In humans, 76% of all lesions were located periungually, whereas in Wistar rats, 67% of lesions were located at the distal end of the digits (P = 0.73). Both had the majority of lesions at the toes and digits: 70.2% versus 65.7% (P = 0.79). The Wistar rat model mirrors human tungiasis in topographic distribution. PMID:22764302

Do foreign direct investment and renewable energy consumption affect the CO2 emissions? New evidence from a panel ARDL approach to Kyoto Annex countries.

PubMed

Mert, Mehmet; Bölük, Gülden

2016-11-01

This study examines the impact of foreign direct investment (FDI) and the potential of renewable energy consumption on carbon dioxide (CO 2 ) emissions in 21 Kyoto countries using an unbalanced panel data. For this purpose, Environmental Kuznets Curve (EKC) hypothesis was tested using panel cointegration analysis. Panel causality tests show that there are significant long-run causalities from the variables to carbon emissions, renewable energy consumption, fossil fuel energy consumption and inflow foreign direct investments. The results of our model support the pollution haloes hypothesis which states that FDI brings in clean technology and improves the environmental standards. However, an inverted U-shaped relationship (EKC) was not supported by the estimated model for the 21 Kyoto countries. This means that economic growth cannot ensure environmental protection itself or environmental goals cannot await economic growth. Another important finding is that renewable energy consumption decreases carbon emissions. Based on the empirical results, some important policy implications emerge. Kyoto countries should stimulate the FDI inflows and usage of renewable energy consumption to mitigate the air pollution and meet the emission targets. This paper provides new insights into environment and energy policies through FDI inclusion.

A case-control study of self-reported health, quality-of-life and general functioning among recent immigrants and age- and sex-matched Swedish-born controls.

PubMed

Löfvander, Monica; Rosenblad, Andreas; Wiklund, Tony; Bennström, Halina; Leppert, Jerzy

2014-12-01

To examine whether new immigrants had inferior quality-of-life, well-being and general functioning compared with Swedish age- and sex-matched controls. A prospective case-control study was designed including immigrants from non-European countries, 18-65 years of age, with recent Permanent Permits to Stay (PPS) in Sweden, and age- and sex-matched Swedish-born (SB) persons from the general population in Västmanland County, Sweden. The General Health Questionnaire (GHQ-12), the brief version of the World Health Organization Quality-of-Life (WHOQOL-BREF) Scale and the General Activity Functioning Assessment Scale (GAF) from DSM-IV were posted (SB), or applied in personal interviews (PPS) with interpreters. Differences between the PPS and SB groups were measured using McNemar's test and Wilcoxon signed-rank test conducted separately for observations at baseline, 6- and 12-month follow-up. There were 93 pairs (mean age 36 years). Persons from Somalia (67%) and Iraq (27%) dominated the PPS group. The differences between the groups were statistically significant for all time points for the Psychological health and Social relationship domains of WHOQOL-BREF, and for the baseline and 6-month follow-up time points of GHQ-12 where the PPS-group had a higher degree of well-being, health and quality-of-life than the SB. This tendency applied for both sexes in the immigrant group. These new immigrants did not have inferior physical or psychological health, quality-of-life, well-being or social functioning compared with their age- and sex-matched Swedish born pairs during a 1-year follow-up. Thus, there is reason to advocate immigrants' fast integration into society. © 2014 the Nordic Societies of Public Health.

The match-to-match variation of match-running in elite female soccer.

PubMed

Trewin, Joshua; Meylan, César; Varley, Matthew C; Cronin, John

2018-02-01

The purpose of this study was to examine the match-to-match variation of match-running in elite female soccer players utilising GPS, using full-match and rolling period analyses. Longitudinal study. Elite female soccer players (n=45) from the same national team were observed during 55 international fixtures across 5 years (2012-2016). Data was analysed using a custom built MS Excel spreadsheet as full-matches and using a rolling 5-min analysis period, for all players who played 90-min matches (files=172). Variation was examined using co-efficient of variation and 90% confidence limits, calculated following log transformation. Total distance per minute exhibited the smallest variation when both the full-match and peak 5-min running periods were examined (CV=6.8-7.2%). Sprint-efforts were the most variable during a full-match (CV=53%), whilst high-speed running per minute exhibited the greatest variation in the post-peak 5-min period (CV=143%). Peak running periods were observed as slightly more variable than full-match analyses, with the post-peak period very-highly variable. Variability of accelerations (CV=17%) and Player Load (CV=14%) was lower than that of high-speed actions. Positional differences were also present, with centre backs exhibiting the greatest variation in high-speed movements (CV=41-65%). Practitioners and researchers should account for within player variability when examining match performances. Identification of peak running periods should be used to assist worst case scenarios. Whilst micro-sensor technology should be further examined as to its viable use within match-analyses. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Stereotactic radiosurgery for brain metastases: a case-matched study comparing treatment results for patients 80 years of age or older versus patients 65-79 years of age.

PubMed

Watanabe, Shinya; Yamamoto, Masaaki; Sato, Yasunori; Kawabe, Takuya; Higuchi, Yoshinori; Kasuya, Hidetoshi; Yamamoto, Tetsuya; Matsumura, Akira; Barfod, Bierta E

2014-11-01

Recently, an increasing number of patients with brain metastases, even patients over 80 years of age, have been treated with stereotactic radiosurgery (SRS). However, there is little information on SRS treatment results for patients with brain metastases 80 years of age and older. The authors undertook this study to reappraise whether SRS treatment results for patients 80 years of age or older differ from those of patients who are 65-79 years old. This was an institutional review board-approved, retrospective cohort study. Among 2552 consecutive brain metastasis patients who underwent SRS during the 1998-2011 period, we studied 165 who were 80 years of age or older (Group A) and 1181 who were age 65-79 years old (Group B). Because of the remarkable disproportion in patient numbers between the 2 groups and considerable differences in pre-SRS clinical factors, the authors conducted a case-matched study using the propensity score matching method. Ultimately, 330 patients (165 from each group, A and B) were selected. For time-to-event outcomes, the Kaplan-Meier method was used to estimate overall survival and competing risk analysis was used to estimate other study end points, as appropriate. Although the case-matched study showed that post-SRS median survival time (MST, months) was shorter in Group A patients (5.3 months, 95% CI 3.9-7.0 months) than in Group B patients (6.9 months, 95% CI 5.0-8.1 months), this difference was not statistically significant (HR 1.147, 95% CI 0.921-1.429, p = 0.22). Incidences of neurological death and deterioration were slightly lower in Group A than in Group B patients (6.3% vs 11.8% and 8.5% vs 13.9%), but these differences did not reach statistical significance (p = 0.11 and p = 0.16). Furthermore, competing risk analyses showed that the 2 groups did not differ significantly in cumulative incidence of local recurrence (HR 0.830, 95% CI 0.268-2.573, p = 0.75), rates of repeat SRS (HR 0.738, 95% CI 0.438-1.242, p = 0.25), or incidence

Comparing the Behavioural Effects of Exogenous Growth Hormone and Melatonin in Young and Old Wistar Rats

PubMed Central

Nicolau, Cristina; Gamundí, Antoni; Fiol, Maria A.; Tresguerres, Jesús A. F.; Akaârir, Mourad; Rial, Rubén V.

2016-01-01

Growth hormone (GH) and melatonin are two hormones with quite different physiological effects. Curiously, their secretion shows parallel and severe age-related reductions. This has promoted many reports for studying the therapeutic supplementation of both hormones in an attempt to avoid or delay the physical, physiological, and psychological decay observed in aged humans and in experimental animals. Interestingly, the effects of the external administration of low doses of GH and of melatonin were surprisingly similar, as both hormones caused significant improvements in the functional capabilities of aged subjects. The present report aims at discerning the eventual difference between cognitive and motor effects of the two hormones when administered to young and aged Wistar rats. The effects were tested in the radial maze, a test highly sensitive to the age-related impairments in working memory and also in the rotarod test, for evaluating the motor coordination. The results showed that both hormones caused clear improvements in both tasks. However, while GH improved the cognitive capacity and, most importantly, the physical stamina, the effects of melatonin should be attributed to its antioxidant, anxiolytic, and neuroprotective properties. PMID:28050228

Behavioral, Ventilatory and Thermoregulatory Responses to Hypercapnia and Hypoxia in the Wistar Audiogenic Rat (WAR) Strain

PubMed Central

Giusti, Humberto; Oliveira, José Antonio; Glass, Mogens Lesner; Garcia-Cairasco, Norberto

2016-01-01

Introduction We investigated the behavioral, respiratory, and thermoregulatory responses elicited by acute exposure to both hypercapnic and hypoxic environments in Wistar audiogenic rats (WARs). The WAR strain represents a genetic animal model of epilepsy. Methods Behavioral analyses were performed using neuroethological methods, and flowcharts were constructed to illustrate behavioral findings. The body plethysmography method was used to obtain pulmonary ventilation (VE) measurements, and body temperature (Tb) measurements were taken via temperature sensors implanted in the abdominal cavities of the animals. Results No significant difference was observed between the WAR and Wistar control group with respect to the thermoregulatory response elicited by exposure to both acute hypercapnia and acute hypoxia (p>0.05). However, we found that the VE of WARs was attenuated relative to that of Wistar control animals during exposure to both hypercapnic (WAR: 133 ± 11% vs. Wistar: 243 ± 23%, p<0.01) and hypoxic conditions (WAR: 138 ± 8% vs. Wistar: 177 ± 8%; p<0.01). In addition, we noted that this ventilatory attenuation was followed by alterations in the behavioral responses of these animals. Conclusions Our results indicate that WARs, a genetic model of epilepsy, have important alterations in their ability to compensate for changes in levels of various arterial blood gasses. WARs present an attenuated ventilatory response to an increased PaCO2 or decreased PaO2, coupled to behavioral changes, which make them a suitable model to further study respiratory risks associated to epilepsy. PMID:27149672

Ex-Premature Infant Boys with Hypospadias are Similar in Size to Age-Matched, Ex-Premature Infant Boys Without Hypospadias

PubMed Central

Hsieh, Michael H.; Alonzo, David G.; Gonzales, Edmond T.; Jones, Eric A.; Cisek, Lars J.; Roth, David R.

2010-01-01

OBJECTIVE Studies have postulated that hypospadias, prematurity, and low birth weight are linked by defects in androgen signaling. To determine whether premature, hypospadiac boys are small and remain so, we compared their size at birth and at hypospadias repair to premature boys who underwent post-neonatal circumcision. METHODS We identified premature boys admitted to Texas Children's Hospital who underwent either hypospadias repair or circumcision after 4 months of age. Age, weight, and height at birth and surgery were recorded. RESULTS Fifty-four boys had hypospadias and 34 did not. For hypospadiac boys, the mean birth weight and age, height, and weight at surgery were lower than for boys without hypospadias. More importantly, length-for-age and weight-for-age percentiles were also lower for hypospadiac boys. When subset analysis was performed on boys younger than 2 years at surgery, however, there were no significant differences in height or weight between hypospadiac and nonhypospadiac boys. CONCLUSION Our series suggests that premature, hypospadiac boys are born smaller than age-matched, non-hypospadiac controls. However, there were no age-corrected size differences between hypospadiac and non-hypospadiac boys at surgery. This implies that hypospadiac boys exhibit postneonatal ‘rebound’ growth. Global growth deficits, if any, do not persist in hypospadiac boys. PMID:20833109

Endoplasmic reticulum stress inhibition reduces hypertension through the preservation of resistance blood vessel structure and function.

PubMed

Carlisle, Rachel E; Werner, Kaitlyn E; Yum, Victoria; Lu, Chao; Tat, Victor; Memon, Muzammil; No, Yejin; Ask, Kjetil; Dickhout, Jeffrey G

2016-08-01

Our purpose was to determine if endoplasmic reticulum stress inhibition lowers blood pressure (BP) in hypertension by correcting vascular dysfunction. The spontaneously hypertensive rat (SHR) was used as a model of human essential hypertension with its normotensive control, the Wistar Kyoto rat. Animals were subjected to endoplasmic reticulum stress inhibition with 4-phenylbutyric acid (4-PBA; 1 g/kg per day, orally) for 5 weeks from 12 weeks of age. BP was measured weekly noninvasively and at endpoint with carotid arterial cannulation. Small mesenteric arteries were removed for vascular studies. Function was assessed with a Mulvany-Halpern style myograph, and structure was assessed by measurement of medial-to-lumen ratio in perfusion fixed vessels as well as three-dimensional confocal reconstruction of vessel wall components. Endoplasmic reticulum stress was assessed by quantitative real time-PCR and western blotting; oxidative stress was assessed by 3-nitrotyrosine and dihydroethidium staining. 4-PBA significantly lowered BP in SHR (vehicle 206.1 ± 4.3 vs. 4-PBA 178.9 ± 3.1, systolic) but not Wistar Kyoto. 4-PBA diminished contractility and augmented endothelial-dependent vasodilation in SHR small mesenteric arteries, as well as reducing media-to-lumen ratio. 4-PBA significantly reduced endoplasmic reticulum stress in SHR resistance vessels. Normotensive resistance vessels, treated with the endoplasmic reticulum stress-inducing agent, tunicamycin, show decreased endothelial-dependent vasodilation; this was improved with 4-PBA treatment. 3-Nitrotyrosine and dihydroethidium staining indicated that endoplasmic reticulum stress leads to reactive oxygen species generation resolvable by 4-PBA treatment. Endoplasmic reticulum stress caused endothelial-mediated vascular dysfunction contributing to elevated BP in the SHR model of human essential hypertension.

Activation of the reticulothalamic cholinergic pathway by the major metabolites of aniracetam.

PubMed

Nakamura, K; Shirane, M

1999-09-10

The aim of the study was to further investigate the effects of aniracetam, a cognition enhancer, and its metabolites on the brain cholinergic system. We measured choline acetyltransferase activity and acetylcholine release using in vivo brain microdialysis in stroke-prone spontaneously hypertensive rats (SHRSP). The enzyme activity in the pons-midbrain and hippocampus, and basal acetylcholine release in the nucleus reticularis thalami were lower in SHRSP than in age-matched Wistar Kyoto rats, indicating central cholinergic deficits in SHRSP. Repeated treatment of aniracetam (50 mg/kg p.o. x 11 for 6 days) preferentially increased the enzyme activity in the thalamus, whereas decreased it in the striatum. Among the metabolites of aniracetam, local perfusion of N-anisoyl-gamma-aminobutyric acid (GABA, 0.1 and/or 1 microM) and p-anisic acid (1 microM) into the nucleus reticularis thalami, dorsal hippocampus and prefrontal cortex of SHRSP produced a significant but delayed increase of acetylcholine release. We failed, however, to find any effect of aniracetam itself. A direct injection of N-anisoyl-GABA (1 nmol) into the pedunculopontine tegmental nucleus of SHRSP enhanced the release in the nucleus reticularis thalami. Thus, these data prove that aniracetam can facilitate central cholinergic neurotransmission via both metabolites. Based on its pharmacokinetic profile, N-anisoyl-GABA may contribute to the clinical effects of aniracetam, mainly by acting on the reticulothalamic cholinergic pathway.

Profilin-1 Promotes the Development of Hypertension-induced Artery Remodeling

PubMed Central

Wang, Yan; Zhang, Jun; Gao, Haiqing; Zhao, Shaohua; Ji, Xiang; Liu, Xiangju; You, Beian; Li, Xiao

2014-01-01

Hypertension is associated with the structural remodeling and stiffening of arteries and is known to increase cardiovascular risk. In the present study, we investigated the effects of overexpression and knock down of profilin-1 on the vascular structural remodeling in spontaneous hypertensive rats (SHRs) using an adenovirus injection to knock down or overexpress profilin-1 mRNA. As a control, blank adenovirus was injected into age-matched SHRs and Wistar-Kyoto rats (WKYs). We quantified arterial structural remodeling through morphological methods, with thoracic aortas stained with hematoxylin–eosin and picosirius red. Western blotting was performed to measure the protein expression of inducible nitric oxide synthase (iNOS) and p38 mitogen-activated protein kinase (p38), and peroxynitrite was quantified by immunohistochemical staining. Overexpression of profilin-1 significantly promoted aortic remodeling, including an increase in vessel size, wall thickness, and collagen content, whereas the knockdown of profilin-1 could reverse these effects. In addition, the expression of phosphorylated p38, iNOS and peroxynitrite was significantly upregulated in SHRs with profilin-1 overexpression along with an increased level of interleukin- 6 (IL-6). These changes could be reversed by knockdown of profilin-1. Our results demonstrate a crucial role for profilin-1 in hypertension-induced arterial structural remodeling at least in part through the p38–iNOS–peroxynitrite pathway. PMID:24399041

Dose-response characteristics of methylphenidate on locomotor behavior and on sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats.

PubMed

Yang, Pamela B; Swann, Alan C; Dafny, Nachum

2006-01-17

Methylphenidate (MPD) is a psychostimulant commonly prescribed for attention deficit/hyperactivity disorder. The mode of action of the brain circuitry responsible for initiating the animals' behavior in response to psychostimulants is not well understood. There is some evidence that psychostimulants activate the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC). The present study was designed to investigate the acute dose-response of MPD (0.6, 2.5, and 10.0 mg/kg) on locomotor behavior and sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats previously implanted with permanent electrodes. For locomotor behavior, adult male Wistar-Kyoto (WKY; n = 39) rats were given saline on experimental day 1 and either saline or an acute injection of MPD (0.6, 2.5, or 10.0 mg/kg, i.p.) on experimental day 2. Locomotor activity was recorded for 2-h post injection on both days using an automated, computerized activity monitoring system. Electrophysiological recordings were also performed in the adult male WKY rats (n = 10). Five to seven days after the rats had recovered from the implantation of electrodes, each rat was placed in a sound-insulated, electrophysiological test chamber where its sensory evoked field potentials were recorded before and after saline and 0.6, 2.5, and 10.0 mg/kg MPD injection. Time interval between injections was 90 min. Results showed an increase in locomotion with dose-response characteristics, while a dose-response decrease in amplitude of the components of sensory evoked field responses of the VTA, NAc, and PFC neurons. For example, the P3 component of the sensory evoked field response of the VTA decreased by 19.8% +/- 7.4% from baseline after treatment of 0.6 mg/kg MPD, 37.8% +/- 5.9% after 2.5 mg/kg MPD, and 56.5% +/- 3.9% after 10 mg/kg MPD. Greater attenuation from baseline was observed in the NAc and PFC. Differences in the intensity of MPD-induced attenuation were also found among

Match running performance and fitness in youth soccer.

PubMed

Buchheit, M; Mendez-Villanueva, A; Simpson, B M; Bourdon, P C

2010-11-01

The activity profiles of highly trained young soccer players were examined in relation to age, playing position and physical capacity. Time-motion analyses (global positioning system) were performed on 77 (U13-U18; fullbacks [FB], centre-backs [CB], midfielders [MD], wide midfielders [W], second strikers [2 (nd)S] and strikers [S]) during 42 international club games. Total distance covered (TD) and very high-intensity activities (VHIA; >16.1 km·h (-1)) were computed during 186 entire player-matches. Physical capacity was assessed via field test measures (e. g., peak running speed during an incremental field test, VVam-eval). Match running performance showed an increasing trend with age ( P<0.001, partial eta-squared (η (2)): 0.20-0.45). When adjusted for age and individual playing time, match running performance was position-dependent ( P<0.001, η (2): 0.13-0.40). MD covered the greater TD; CB the lowest ( P<0.05). Distance for VHIA was lower for CB compared with all other positions ( P<0.05); W and S displayed the highest VHIA ( P<0.05). Relationships between match running performance and physical capacities were position-dependent, with poor or non-significant correlations within FB, CB, MD and W (e. g., VHIA vs. VVam-eval: R=0.06 in FB) but large associations within 2 (nd)S and S positions (e. g., VHIA vs. VVam-eval: R=0.70 in 2 (nd)S). In highly trained young soccer players, the importance of fitness level as a determinant of match running performance should be regarded as a function of playing position.

Endocannabinoids Acting at Cannabinoid-1 Receptors Regulate Cardiovascular Function in Hypertension

PubMed Central

Bátkai, Sándor; Pacher, Pál; Osei-Hyiaman, Douglas; Radaeva, Svetlana; Liu, Jie; Harvey-White, Judith; Offertáler, László; Mackie, Ken; Audrey Rudd, M.; Bukoski, Richard D.; Kunos, George

2009-01-01

Background Endocannabinoids are novel lipid mediators with hypotensive and cardiodepressor activity. Here, we examined the possible role of the endocannabinergic system in cardiovascular regulation in hypertension. Methods and Results In spontaneously hypertensive rats (SHR), cannabinoid-1 receptor (CB1) antagonists increase blood pressure and left ventricular contractile performance. Conversely, preventing the degradation of the endocannabinoid anandamide by an inhibitor of fatty acid amidohydrolase reduces blood pressure, cardiac contractility, and vascular resistance to levels in normotensive rats, and these effects are prevented by CB1 antagonists. Similar changes are observed in 2 additional models of hypertension, whereas in normotensive control rats, the same parameters remain unaffected by any of these treatments. CB1 agonists lower blood pressure much more in SHR than in normotensive Wistar-Kyoto rats, and the expression of CB1 is increased in heart and aortic endothelium of SHR compared with Wistar-Kyoto rats. Conclusions We conclude that endocannabinoids tonically suppress cardiac contractility in hypertension and that enhancing the CB1-mediated cardiodepressor and vasodilator effects of endogenous anandamide by blocking its hydrolysis can normalize blood pressure. Targeting the endocannabinoid system offers novel therapeutic strategies in the treatment of hypertension. PMID:15451779

Serum 25-hydroxyvitamin D concentrations in dogs with osteosarcoma do not differ from those of age- and weight-matched control dogs.

PubMed

Willcox, Jennifer L; Hammett-Stabler, Catherine; Hauck, Marlene L

2016-11-01

Vitamin D concentrations show an inverse correlation with incidence of certain tumors in people and dogs. Additionally, human osteosarcoma has been associated with dysregulation of vitamin D-dependent pathways. The study objective was to compare serum 25-hydroxyvitamin D 2 and 25-hydroxyvitamin D 3 in 20 dogs with osteosarcoma to age- and weight-matched control dogs. We hypothesized that dogs with osteosarcoma would have lower serum 25-hydroxyvitamin D than control dogs. The mean 25-hydroxyvitamin D 3 concentrations for dogs with osteosarcoma and matched-controls were 34.95 ng/mL and 33.85 ng/mL, respectively (P = 0.784). Based on these data, 25-hydroxyvitamin D insufficiency might not be important in the pathogenesis of canine osteosarcoma. Published by Elsevier Ltd.

Sub-chronic oral toxicity of Cuminum cyminum L.'s essential oil in female Wistar rats.

PubMed

Taghizadeh, Mohsen; Ostad, Seyed Naser; Asemi, Zatollah; Mahboubi, Mohaddese; Hejazi, Sara; Sharafati-Chaleshtori, Reza; Rashidi, Aliakbar; Akbari, Hosein; Sharifi, Nasrin

2017-08-01

The current study was performed to evaluate the toxicity of Cuminum cyminum L. (C. cyminum)'s essential oil after 23 days and 45 days of repeated oral administration in female Wistar rats. A total of 80 healthy female Wistar rats were randomly selected and divided into 4 groups. The rats were gavaged with C. cyminum's essential oil at dose levels of 0, 250, 500 and 1000 mg/kg/day. Clinical signs, body weight, hematology, serum biochemistry and organ histopathology were assessed once after 23 days and again after 45 days passed from the start of the intervention. Oral administration of C. cyminum's essential oil had no observed adverse effects on clinical signs, mortality, body weight, hematology, biochemistry and organ histology (liver, kidneys, spleen and lungs) in a sample of healthy female Wistar rats after 23 days and 45 days from the start of the study. However, an increase in serum levels of alanine transaminase (ALT) was found only at dose level of 1000 mg/kg/d C. cyminum's essential oil, after the 23-days interval. We conservatively defined the non-observed adverse effect level (NOAEL) for C. cyminum's essential oil as 500 mg/kg/d in female Wistar rats. The present study results should be treated with cautious in terms of the other organs' toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Early and intensive nutritional strategy combining parenteral and enteral feeding promotes neurodevelopment and growth at 18months of corrected age and 3years of age in extremely low birth weight infants.

PubMed

Ohnishi, Satoshi; Ichiba, Hiroyuki; Tanaka, Yuko; Harada, Sayaka; Matsumura, Hisako; Kan, Ayako; Asada, Yuki; Shintaku, Haruo

2016-09-01

To evaluate whether aggressive nutrition can improve long-term neurodevelopmental outcomes and growth in extremely low birth weight (ELBW) infants born appropriate for gestational age (AGA). This single-center cohort study included 137 ELBW AGA infants born in two epochs. The first group received standard nutrition (SN; n=79) consisting of amino acids started at 0.5g/kg/day on Day 4 of life and increased to 1.0g/kg/day. The second aggressive nutrition (AN) group received amino acids started at 1.5-2.0g/kg/day within 24h of life and increased to 3.5g/kg/day. Parenteral and enteral feedings were combined in both groups. Neurodevelopmental outcomes by the Kyoto Scale of Psychological Development and growth were followed up to 18months of corrected age or 3years of age and compared by univariate and multivariate analyses. Baseline characteristics were similar between the two groups. At 3years of age, AN children had a significantly greater mean value of head circumference, but not length or weight, than SN children (49.1 vs 48.0cm, p=0.014). The cognitive-adaptive (C-A) score in the AN group was also significantly higher than that in the SN group (98.3 vs 91.9 at 18months, p=0.039 and 89.5 vs 83.1 at 3years, p=0.047). AN infants born ≥26weeks of gestation were less likely to develop borderline disability in C-A, language-social and overall developmental scores compared to gestational age-matched SN infants. Parenteral and enteral AN after birth improved the long-term cognitive neurodevelopment in ELBW AGA infants, especially in those born ≥26weeks of gestational age, however results need to be confirmed in a larger, multi-site randomized trial. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Influence of dyadic matching of affect on infant self-regulation.

PubMed

Noe, Daniela; Schluckwerder, Sabine; Reck, Corinna

2015-01-01

Affective behavioural matching during face-to-face interaction fosters the transition from mutual regulation to infant self-regulation. Optimum midrange models of mother-infant interaction hold that moderate degrees of dyadic matching facilitate infant socio-emotional development. The aim of this study was to examine which degree of dyadic matching is most beneficial for infant self-regulation. To evaluate this model, 3 groups of highly, midrange and poorly matched dyads were created from a mixed sample of 68 dyads with healthy and post-partum depressed mothers and their infants (age range = 1-8 months, mean age = 3.9 months). Mother-infant interactions were videotaped in the face-to-face still-face paradigm (FFSF) and micro-analytically coded. Specifically, the relation between affective behavioural matching in FFSF play and infant positive and negative affect in FFSF still face and FFSF reunion was explored. Contrary to our expectation, we found a monotonous trend for all groups: the more matching in FFSF play, the more positive and less negative affect the infant showed in FFSF still face and FFSF reunion, respectively. The present findings further illuminate the association between different degrees of dyadic matching in early mother-infant interaction and infant self-regulation. Further research should focus on the integration and replication of findings and conceptual approaches to further evaluate and refine the concept of midrange matching and make it applicable to therapeutic work with mothers and their infants.

A STUDY OF CHANGES IN DEFORMATION AND METABOLISM IN LEFT VENTRICLE AS A FUNCTION OF HYPERTROPHY IN SPONTANEOUS HYPERTENSIVE RATS USING MICROPET TECHNOLOGY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gullberg, Grant, T; Huesman, Ronald, H; Reutter, Bryan, W

Problem: In the case of hypertrophy caused by pressure overload (hypertension) there is an increase in cardiac mass and modification cardiac metabolism. Aim: This study was designed to study the changes in glucose metabolism, ejection fraction, and deformation in the left ventricle with the progression of hypertrophy in spontaneous hypertensive rats (SHR). Methods: Dynamic PET data were acquired using the microPET II at UC Davis. Two rats were imaged at 10-week intervals for 18 months. Each time a dose of approximately 1- 1.5 mCi of F-18-FDG was injected into a normotensive Wistar Kyoto (WKY) rat and the same dose wasmore » injected into a SHR rat. Each rat was imaged using a gated dynamic acquisition for 80 minutes acquiring list mode data with cardiac gating of approximately 600-900 million total counts. For the analysis of glucose of metabolism, the list mode data were histogrammed into a dynamic sequence (42 frames over 80 mins). For each time frame, projection data of 1203 140x210 sinograms of 0.582 mm bins were formed by summing the last three gates before and one after the R-wave trigger to correspond to the diastolic phase of the cardiac cycle. Dynamic sequences of 128x128x83 matrices of 0.4x0.4x0.582 mm3 voxels in x, y, and z were reconstructed using an iterative MAP reconstruction which used a prior that penalized the high frequency components of the reconstruction using appropriate weighting between 26 nearest neighboring voxels. Time activity curves were generated from the dynamic reconstructed sequence for the blood and left ventricular tissue regions of interest which were fit to a 2-compartment model to obtain a least squares fit for the kinetic parameters. For the analysis of deformation, the list mode data were histogrammed into 8 gates of the cardiac cycle, each gate was the total sum of the later 60 mins of the 80 min acquisition. Images of 128x128x83 matrices for each gate were reconstructed using the same iterative MAP reconstruction used to

Ultrastructural and cellular basis for the development of abnormal myocardial mechanics during the transition from hypertension to heart failure.

PubMed

Shah, Sanjiv J; Aistrup, Gary L; Gupta, Deepak K; O'Toole, Matthew J; Nahhas, Amanda F; Schuster, Daniel; Chirayil, Nimi; Bassi, Nikhil; Ramakrishna, Satvik; Beussink, Lauren; Misener, Sol; Kane, Bonnie; Wang, David; Randolph, Blake; Ito, Aiko; Wu, Megan; Akintilo, Lisa; Mongkolrattanothai, Thitipong; Reddy, Mahendra; Kumar, Manvinder; Arora, Rishi; Ng, Jason; Wasserstrom, J Andrew

2014-01-01

Although the development of abnormal myocardial mechanics represents a key step during the transition from hypertension to overt heart failure (HF), the underlying ultrastructural and cellular basis of abnormal myocardial mechanics remains unclear. We therefore investigated how changes in transverse (T)-tubule organization and the resulting altered intracellular Ca(2+) cycling in large cell populations underlie the development of abnormal myocardial mechanics in a model of chronic hypertension. Hearts from spontaneously hypertensive rats (SHRs; n = 72) were studied at different ages and stages of hypertensive heart disease and early HF and were compared with age-matched control (Wistar-Kyoto) rats (n = 34). Echocardiography, including tissue Doppler and speckle-tracking analysis, was performed just before euthanization, after which T-tubule organization and Ca(2+) transients were studied using confocal microscopy. In SHRs, abnormalities in myocardial mechanics occurred early in response to hypertension, before the development of overt systolic dysfunction and HF. Reduced longitudinal, circumferential, and radial strain as well as reduced tissue Doppler early diastolic tissue velocities occurred in concert with T-tubule disorganization and impaired Ca(2+) cycling, all of which preceded the development of cardiac fibrosis. The time to peak of intracellular Ca(2+) transients was slowed due to T-tubule disruption, providing a link between declining cell ultrastructure and abnormal myocardial mechanics. In conclusion, subclinical abnormalities in myocardial mechanics occur early in response to hypertension and coincide with the development of T-tubule disorganization and impaired intracellular Ca(2+) cycling. These changes occur before the development of significant cardiac fibrosis and precede the development of overt cardiac dysfunction and HF.

Social play behavior, ultrasonic vocalizations and their modulation by morphine and amphetamine in Wistar and Sprague-Dawley rats.

PubMed

Manduca, Antonia; Campolongo, Patrizia; Palmery, Maura; Vanderschuren, Louk J M J; Cuomo, Vincenzo; Trezza, Viviana

2014-04-01

Social play behavior is the most characteristic social behavior in young mammals. It is highly rewarding and crucial for proper neurobehavioral development. Despite the importance of genetic factors in normal and pathological social behaviors, little information is available about strain influences on social play. The aim of this study was to investigate differences in social play behavior, 50-kHz ultrasonic vocalizations (USVs) and their modulation by acute morphine and amphetamine administration in two rat strains widely used in behavioral pharmacology studies, i.e., Wistar and Sprague-Dawley rats. Sprague-Dawley rats showed higher levels of social play than Wistar rats. In both strains, no correlation was found between the performance of social behaviors and the emission of 50-kHz USVs. In Wistar and Sprague-Dawley rats, morphine increased and amphetamine decreased social play. The effects of morphine, however, were more pronounced in Wistar than Sprague-Dawley animals. In both strains, morphine did not affect USV emission, while amphetamine increased it during cage exploration. In Sprague-Dawley rats only, amphetamine decreased USVs during social interaction. Wistar and Sprague-Dawley rats differ in their absolute levels of social play behavior and 50-kHz USVs, and quantitative differences exist in their response to pharmacological manipulations of social play. The emission of 50-kHz USVs and the behavioral parameters thought to reflect rewarding social interactions in adolescent rats are dissociable.

Employment Status, Quality of Matching, and Retirement in Korea: Evidence from Korean Longitudinal Study of Aging1

PubMed Central

Lee, Chulhee; Lee, Jinkook

2013-01-01

This paper explores the differing probabilities of retirement for self-employed and wage-and-salary workers. It finds self-employed workers are less likely to retire than wage-and-salary ones, and that differences in retirement incomes, health, productivity, job characteristics, and compulsory retirement practices do not explain the disparity. The difference between self-employed and wage-and-salary workers in the quality of matching between the job and the worker (i.e., between required and desired amount of work) explains the later retirement of the self-employed. We note the implications of these findings for labor-force participation at older ages and how policies might boost employment of the elderly. PMID:23935768

Heart rate autonomic regulation system at rest and during paced breathing among patients with CRPS as compared to age-matched healthy controls.

PubMed

Bartur, Gadi; Vatine, Jean-Jacques; Raphaely-Beer, Noa; Peleg, Sara; Katz-Leurer, Michal

2014-09-01

The objective of this study is to assess the autonomic nerve heart rate regulation system at rest and its immediate response to paced breathing among patients with complex regional pain syndrome (CRPS) as compared with age-matched healthy controls. Quasiexperimental. Outpatient clinic. Ten patients with CRPS and 10 age- and sex-matched controls. Participants underwent Holter ECG (NorthEast Monitoring, Inc., Maynard, MA, USA) recording during rest and biofeedback-paced breathing session. Heart rate variability (HRV), time, and frequency measures were assessed. HRV and time domain values were significantly lower at rest among patients with CRPS as compared with controls. A significant association was noted between pain rank and HRV frequency measures at rest and during paced breathing; although both groups reduced breathing rate significantly during paced breathing, HRV time domain parameters increased only among the control group. The increased heart rate and decreased HRV at rest in patients with CRPS suggest a general autonomic imbalance. The inability of the patients to increase HRV time domain values during paced breathing may suggest that these patients have sustained stress response with minimal changeability in response to slow-paced breathing stimuli. Wiley Periodicals, Inc.

Daytime mother-calf relationships in reticulated giraffes (Giraffa cameloparadalis reticulate) at the Kyoto City Zoo.

PubMed

Nakamichi, Masayuki; Murata, Chisa; Eto, Ryo; Takagi, Naoko; Yamada, Kazunori

2015-01-01

The present study quantitatively assesses the relationships between a reticulated giraffe mother and her first- and second-born calves during the first 22 months of the older calf's and the first 12 months of the younger calf's life at the Kyoto City Zoo, Japan. The mother permitted her calves to suckle at over 70% of their suckling attempts in the first month after their births, and the calves ceased suckling spontaneously in 65 to 70% of the suckling bouts. From the second month on, she showed a clear tendency to reject the calves' suckling attempts and terminated almost all of their suckling bouts, which resulted in approximately 60 sec or less of suckling duration per bout. The frequency of proximity between the mother and her calves remained at 20 to 30% throughout the first year, with no apparent developmental changes being evident. The mother was mainly responsible for terminating proximity by walking away from her calves throughout their first year after birth, while both calves were mainly responsible for attempting proximity by approaching their mother after reaching 2 months of age. Our study also showed that the giraffe mother became pregnant again while nursing her calves and ceased lactation (i.e., weaned the calves) before the fetus's growth started accelerating. © 2015 Wiley Periodicals, Inc.

Serum levels of advanced glycation end-products (AGEs) and the decoy soluble receptor for AGEs (sRAGE) can identify non-alcoholic fatty liver disease in age-, sex- and BMI-matched normo-glycemic adults.

PubMed

Palma-Duran, Susana A; Kontogianni, Meropi D; Vlassopoulos, Antonis; Zhao, Shudong; Margariti, Aikaterini; Georgoulis, Michael; Papatheodoridis, George; Combet, Emilie

2018-06-01

Non-alcoholic fatty liver disease (NAFLD) is a serious health problem affecting ~25% of the global population. While NAFLD pathogenesis is still unclear, multiple NAFLD parameters, including reduced insulin sensitivity, impaired glucose metabolism and increased oxidative stress are hypothesised to foster the formation of advanced glycation end-products (AGEs). Given the link of AGEs with end organ damage, there is scope to examine the role of the AGE/RAGE axis activation in liver injury and NAFLD. Age, sex and body mass index matched normo-glycemic NAFLD adults (n = 58) and healthy controls (n = 58) were enrolled in the study. AGEs were analysed by liquid chromatography-mass spectrometry (CML, CEL), fluorescence (pentosidine, AGE fluorescence), colorimetry (fructosamine) and ELISA (sRAGE). Their association with liver function, inflammation, fibrosis and stage of NAFLD was examined. Early and advanced glycation end-products, except N ε -carboxymethyl-L-lysine (CML), were 10-30% higher, sRAGE levels 1.7-fold lower, and glycation/sRAGE ratios 4-fold higher in the NAFLD cases compared to controls. While AGEs presented weak to moderate correlations with indices of liver function and damage (AST/ALT, HOMA-IR, TNF-α and TGF-β1), including sRAGE to characterize the AGEs/sRAGE axis strengthened the associations observed. High glycation/sRAGE ratios were associated with 1.3 to 14-fold likelihood of lower AST/ALT ratios. The sum of AGEs/sRAGE ratios accurately distinguished between healthy controls and NAFLD patients (area under the curve of 0.85). Elevated AGEs/sRAGE (>7.8 mmol/pmol) was associated with a 12-fold likelihood of the presence of NAFLD. These findings strengthen the involvement of AGEs-RAGE axis in liver injury and the pathogenesis of NAFLD. Copyright © 2018 Elsevier Inc. All rights reserved.

78 FR 73195 - Privacy Act of 1974: CMS Computer Matching Program Match No. 2013-01; HHS Computer Matching...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-05

.... Description of the Matching Program A. General The Computer Matching and Privacy Protection Act of 1988 (Pub... 1974: CMS Computer Matching Program Match No. 2013-01; HHS Computer Matching Program Match No. 1312...). ACTION: Notice of Computer Matching Program (CMP). SUMMARY: In accordance with the requirements of the...

RotaTeq (sanofi pasteur/Wistar Institute/Children's Hospital of Philadelphia).

PubMed

Desselberger, Ulrich

2005-02-01

Sanofi pasteur MSD (a joint venture between Merck & Co and sanofi pasteur (formerly Aventis Pasteur)), in collaboration with the Wistar Institute and the Children's Hospital of Philadelphia, is developing RotaTeq, an oral liquid pentavalent vaccine for the potential prevention of rotavirus infection-related disorders, such as infant diarrhea and malabsorption. Phase III trials had commenced by March 2001.

Spontaneous pituitary tumors in the Wistar/Furth/Ico rat strain. An animal model of human prolactin adenoma.

PubMed Central

Trouillas, J.; Girod, C.; Claustrat, B.; Curé, M.; Dubois, M. P.

1982-01-01

Twenty-three spontaneous pituitary tumors in 58 rats of Wistar/Furth/Ico strain were studied. The incidence is 38% in rats older than 10 months; it rises with age, with a maximum at 28-32 months (68.7%) and is higher in females (71.4%) than in males (35%) over 17 months. Light-microscopic and immunocytochemical studies revealed 20 prolactinomas in 19 rats (19/58, 32.7%) and 3 spongiocytic nonimmunostaining adenomas (3/58, 5.2%). The prolactinoma is often hemorrhagic. The cells, often arranged in sheets and agranular, are mostly positive with anti-rat prolactin (rPRL) serum. They have few polymorph granules and a well-developed rough endoplasmic reticulum. In the spongiocytic adenoma, the cells are arranged in cords. Their cytoplasm is slightly vacuolated. In prolactinoma-bearing rats, the mean plasma PRL value was 213 +/- 72.5 microgram/1 (SEM) (N = 15 +/- 1.8 microgram/1 [SEM]). A linear correlation was found between the logarithm of the tumoral pituitary weight or of the tumor size and the logarithm of the prolactinemia. Because of the analogies between these rat prolactinomas and 57 human prolactinomas, the Wistar/Furth/Ico rat strain is considered as a good animal model. Images Figure 14 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 12 Figure 13 PMID:7124908

Comparison of Point Matching Techniques for Road Network Matching

NASA Astrophysics Data System (ADS)

Hackeloeer, A.; Klasing, K.; Krisp, J. M.; Meng, L.

2013-05-01

Map conflation investigates the unique identification of geographical entities across different maps depicting the same geographic region. It involves a matching process which aims to find commonalities between geographic features. A specific subdomain of conflation called Road Network Matching establishes correspondences between road networks of different maps on multiple layers of abstraction, ranging from elementary point locations to high-level structures such as road segments or even subgraphs derived from the induced graph of a road network. The process of identifying points located on different maps by means of geometrical, topological and semantical information is called point matching. This paper provides an overview of various techniques for point matching, which is a fundamental requirement for subsequent matching steps focusing on complex high-level entities in geospatial networks. Common point matching approaches as well as certain combinations of these are described, classified and evaluated. Furthermore, a novel similarity metric called the Exact Angular Index is introduced, which considers both topological and geometrical aspects. The results offer a basis for further research on a bottom-up matching process for complex map features, which must rely upon findings derived from suitable point matching algorithms. In the context of Road Network Matching, reliable point matches provide an immediate starting point for finding matches between line segments describing the geometry and topology of road networks, which may in turn be used for performing a structural high-level matching on the network level.

Functional Aspects of Gait in Essential Tremor: A Comparison with Age-Matched Parkinson's Disease Cases, Dystonia Cases, and Controls.

PubMed

Louis, Elan D; Rao, Ashwini K

2015-01-01

An understanding of the functional aspects of gait and balance has wide ramifications. Individuals with balance disorders often restrict physical activity, travel, and social commitments to avoid falling, and loss of balance confidence, itself, is a source of disability. We studied the functional aspects of gait in patients with essential tremor (ET), placing their findings within the context of two other neurological disorders (Parkinson's disease [PD] and dystonia) and comparing them with age-matched controls. We administered the six-item Activities of Balance Confidence (ABC-6) Scale and collected data on number of falls and near-falls, and use of walking aids in 422 participants (126 ET, 77 PD, 46 dystonia, 173 controls). Balance confidence was lowest in PD, intermediate in ET, and relatively preserved in dystonia compared with controls. This ordering reoccurred for each of the six ABC-6 items. The number of near-falls and falls followed a similar ordering. Use of canes, walkers, and wheelchairs was elevated in ET and even greater in PD. Several measures of balance confidence (ABC-6 items 1, 4, 5, and 6) were lower in torticollis cases than in those with blepharospasm, although the two groups did not differ with respect to falls or use of walking aids. Lower balance confidence, increased falls, and greater need for walking aids are variably features of a range of movement disorder patients compared to age-matched controls. While most marked among PD patients, these issues affected ET patients as well and, to a small degree, some patients with dystonia.

Intermodal Matching of Emotional Expressions in Young Children with Autism

ERIC Educational Resources Information Center

Kahana-Kalman, Ronit; Goldman, Sylvie

2008-01-01

This study examined the ability of young children with autism spectrum disorders (ASD) to detect affective correspondences between facial and vocal expressions of emotion using an intermodal matching paradigm. Four-year-old children with ASD (n = 18) and their age-matched normally developing peers (n = 18) were presented pairs of videotaped facial…

Physiological responses and match characteristics in professional tennis players during a one-hour simulated tennis match

PubMed Central

Şenel, Ömer; Arslan, Erşan; Can, Sema

2016-01-01

Abstract The purpose of this study was to investigate the effects of serve and return game situations on physiological responses and match characteristics in professional male tennis players during one hour-long simulated singles tennis matches. Ten internationally ranked tennis players (age 22.2 ± 2.8 years; body height 180.7 ± 4.4 cm; body mass 75.9 ± 8.9 kg) participated in this study. Their physiological responses were measured using two portable analyzers during indoor hard court matches. Ratings of perceived exertion were also determined at the end of the game. The variables describing the characteristics of the matches determined from video recordings were: (a) duration of rallies; (b) rest time; (c) work-to-rest ratio; (d) effective playing time; and (d) strokes per rally. Significant differences (p<0.05) were found between serving and returning conditions in an hour-long simulated singles tennis match in terms of oxygen uptake, a heart rate, ratings of perceived exertion, pulmonary ventilation, respiration frequency and a respiratory gas exchange ratio. In addition, both the heart rate and ratings of perceived exertion responses were moderately correlated with the duration of rallies and strokes per rally (r = 0.60 to 0.26; p<0.05). Taken together, these results indicate that the serve game situation has a significant effect on the physiological response in an hour-long simulated tennis match between professional male tennis players. These findings might be used for the physiological adaptations required for tennis-specific aerobic endurance. PMID:28149371

Haematocrit, hypertension and smoking in patients with transient ischaemic attacks and in age and sex matched controls.

PubMed Central

Harrison, M J; Pollock, S; Thomas, D; Marshall, J

1982-01-01

The blood pressure, smoking habit and haemotocrit of 154 patients with transient ischaemic attacks and 191 age-and sex-matched neurological controls were studied. Regression analysis revealed that the haematocrit value was related to both systolic and diastolic blood pressure, and to smoking. Smoking elevated the haematocrit by 1.9 +/- 0.59 in males and by 2.18 +/- 0.68 in females. When these associations were allowed for there was still evidence of a higher haematocrit in patients with transient ischaemic attacks (plus 1.44 +/- 0.56 in males and 0.75 +/- 0.75 in females p less than 0.02). The role of an elevated haematocrit in the pathogenesis of cerebrovascular disease and its management are briefly discussed. PMID:7119818

Performance of Disease Risk Score Matching in Nested Case-Control Studies: A Simulation Study.

PubMed

Desai, Rishi J; Glynn, Robert J; Wang, Shirley; Gagne, Joshua J

2016-05-15

In a case-control study, matching on a disease risk score (DRS), which includes many confounders, should theoretically result in greater precision than matching on only a few confounders; however, this has not been investigated. We simulated 1,000 hypothetical cohorts with a binary exposure, a time-to-event outcome, and 13 covariates. Each cohort comprised 2 subcohorts of 10,000 patients each: a historical subcohort and a concurrent subcohort. DRS were estimated in the historical subcohorts and applied to the concurrent subcohorts. Nested case-control studies were conducted in the concurrent subcohorts using incidence density sampling with 2 strategies-matching on age and sex, with adjustment for additional confounders, and matching on DRS-followed by conditional logistic regression for 9 outcome-exposure incidence scenarios. In all scenarios, DRS matching yielded lower average standard errors and mean squared errors than did matching on age and sex. In 6 scenarios, DRS matching also resulted in greater empirical power. DRS matching resulted in less relative bias than did matching on age and sex at lower outcome incidences but more relative bias at higher incidences. Post-hoc analysis revealed that the effect of DRS model misspecification might be more pronounced at higher outcome incidences, resulting in higher relative bias. These results suggest that DRS matching might increase the statistical efficiency of case-control studies, particularly when the outcome is rare. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Testing a Matching Hypothesis for Emerging Adults in Project MATCH: During-Treatment and One-Year Outcomes

PubMed Central

Davis, Jordan P.; Bergman, Brandon G.; Smith, Douglas C.; Kelly, John F.

2017-01-01

Objective: Compared with older adults, emerging adults (18-29 years old) entering treatment typically have less severe alcohol use consequences. Also, their unique clinical presentations (e.g., modest initial abstinence motivation) and developmental contexts (e.g., drinking-rich social networks) may make a straightforward implementation of treatments developed for adults less effective. Yet, this has seldom been examined empirically. This study was a secondary analysis of Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) data examining (a) overall differences between emerging adults and older adults (≥30 years old) on outcomes during treatment and at 1-year follow-up, and (b) whether emerging adults had poorer outcomes on any of the three Project MATCH treatments in particular. Method: Participants were 267 emerging adults and 1,459 older adults randomly assigned to individually delivered cognitive-behavioral therapy (CBT), motivational enhancement therapy (MET), or 12-step facilitation (TSF). Multilevel growth curve models tested differences on percentage of days abstinent (PDA) and drinks per drinking day (DDD) by age group and treatment assignment. Results: During treatment, compared with older adults, emerging adults reported more DDD but similar PDA. Further, emerging adults assigned to TSF had less PDA and more DDD than emerging adults and older adults assigned to CBT or MET during treatment (i.e., emerging adults in TSF has poorer outcomes initially), but this matching effect was not evident at 1-year follow-up. Conclusions: This study is among the first to test age group differences across three psychosocial interventions shown to be efficacious treatments for alcohol use disorder. Although emerging adults generally did as well as their older counterparts, they may require a more developmentally sensitive approach to bolster TSF effects during treatment. PMID:27936374

Characteristics of the personal and environmental components of person-environment fit in very old age: a comparison between people with self-reported Parkinson's disease and matched controls.

PubMed

Slaug, Björn; Nilsson, Maria H; Iwarsson, Susanne

2013-12-01

To investigate differences and similarities in person-environment (P-E) fit problems between very old people with self-reported Parkinson's disease (PD) and matched controls. Data collected for the cross-national ENABLE-AGE Survey Study were used to identify people with self-reported PD (n = 20), and to select three matched controls per individual (n = 60). The matching criteria were age (mean = 82 years), sex, country, and type of housing. The data analysis targeted P-E fit (i.e. accessibility) problems, including studying the personal and environmental components separately. The personal component was analyzed in terms of functional limitations, and the environmental component in terms of physical environmental barriers. In comparison to the matched controls, the participants with PD had more functional limitations, used more mobility devices and were subjected to more P-E fit problems, though the number of environmental barriers did not differ from the controls. In the PD sample, P-E fit problems were significantly stronger associated with poor balance and incoordination, and the environmental barriers that generated the most severe P-E fit problems were more often located to the exterior surroundings of the housing compared to the controls. The novel contribution of this explorative study is the demonstration of the type of knowledge that can be generated by unfolding and comparing the composition of P-E fit (accessibility) problems among people with self-reported PD as compared with matched controls. The knowledge thereby generated can be used to develop more targeted rehabilitation approaches, efficient housing adaptation services and societal planning for people with neurodegenerative disorders.

Privacy-preserving matching of similar patients.

PubMed

Vatsalan, Dinusha; Christen, Peter

2016-02-01

The identification of similar entities represented by records in different databases has drawn considerable attention in many application areas, including in the health domain. One important type of entity matching application that is vital for quality healthcare analytics is the identification of similar patients, known as similar patient matching. A key component of identifying similar records is the calculation of similarity of the values in attributes (fields) between these records. Due to increasing privacy and confidentiality concerns, using the actual attribute values of patient records to identify similar records across different organizations is becoming non-trivial because the attributes in such records often contain highly sensitive information such as personal and medical details of patients. Therefore, the matching needs to be based on masked (encoded) values while being effective and efficient to allow matching of large databases. Bloom filter encoding has widely been used as an efficient masking technique for privacy-preserving matching of string and categorical values. However, no work on Bloom filter-based masking of numerical data, such as integer (e.g. age), floating point (e.g. body mass index), and modulus (numbers wrap around upon reaching a certain value, e.g. date and time), which are commonly required in the health domain, has been presented in the literature. We propose a framework with novel methods for masking numerical data using Bloom filters, thereby facilitating the calculation of similarities between records. We conduct an empirical study on publicly available real-world datasets which shows that our framework provides efficient masking and achieves similar matching accuracy compared to the matching of actual unencoded patient records. Copyright © 2015 Elsevier Inc. All rights reserved.

Matching a Distribution by Matching Quantiles Estimation

PubMed Central

Sgouropoulos, Nikolaos; Yao, Qiwei; Yastremiz, Claudia

2015-01-01

Motivated by the problem of selecting representative portfolios for backtesting counterparty credit risks, we propose a matching quantiles estimation (MQE) method for matching a target distribution by that of a linear combination of a set of random variables. An iterative procedure based on the ordinary least-squares estimation (OLS) is proposed to compute MQE. MQE can be easily modified by adding a LASSO penalty term if a sparse representation is desired, or by restricting the matching within certain range of quantiles to match a part of the target distribution. The convergence of the algorithm and the asymptotic properties of the estimation, both with or without LASSO, are established. A measure and an associated statistical test are proposed to assess the goodness-of-match. The finite sample properties are illustrated by simulation. An application in selecting a counterparty representative portfolio with a real dataset is reported. The proposed MQE also finds applications in portfolio tracking, which demonstrates the usefulness of combining MQE with LASSO. PMID:26692592

Proceedings of the International Symposium on Multiple-Valued Logic (13th) Held at Kyoto, Japan on May 23-25, 1983.

DTIC Science & Technology

1983-05-01

would like to thank the members of the Organizing Committee of ISMVL-Japan, listed on page vii of this Proceedings, for their generous support. Hisashi ...8217 °. °- . ’. . 6% Organizing Commnittee I *Chairman: Hisashi Mine Department of Applied Mathematics and Physics Kcyoto University, Kyoto...Masayuki Kimura (Tohoku University, Japan) Tadahiro Kitahashi (Toyohashi University of Technology, Japan) Yoshiaki Koga (National Defense Academy, Japan

Factors Affecting Match Outcome in Elite Australian Football: A 14-Year Analysis.

PubMed

Lazarus, Brendan H; Hopkins, William G; Stewart, Andrew M; Aughey, Robert J

2018-02-01

Effects of fixture and team characteristics on match outcome in elite Australian football were quantified using data accessed at AFLtables.com for 5109 matches for seasons 2000 to 2013. Aspects of each match included number of days' break between matches (≤7 d vs ≥8 d), location (home vs away), travel status (travel vs no travel), and differences between opposing teams' mean age, body mass, and height (expressed as quintiles). A logistic-regression version of the generalized mixed linear model estimated each effect, which was assessed with magnitude-based inference using 1 extra win or loss in every 10 matches as the smallest important change. For every 10 matches played, the effects were days' break, 0.1 ± 0.3 (90% CL) wins; playing away, 1.5 ± 0.6 losses; traveling, 0.7 ± 0.6 losses; and being in the oldest, heaviest, or shortest, quintile, 1.9 ± 0.4, 1.3 ± 0.4, and 0.4 ± 0.4 wins, respectively. The effects of age and body-mass difference were not reduced substantially when adjusted for each other. All effects were clear, mostly at the 99% level. The effects of playing away, travel, and age difference were not unexpected, but the trivial effect of days' break and the advantage of a heavier team will challenge current notions about balancing training with recovery and about team selection.

Finding Major Patterns of Aging Process by Data Synchronization

NASA Astrophysics Data System (ADS)

Miyano, Takaya; Tsutsui, Takako

We developed a method for extracting feature patterns from multivariate data using a network of coupled phase oscillators subject to an analogue of the Kuramoto model for collective synchronization. Our method may be called data synchronization. We applied data synchronization to the care-needs-certification data, provided by Otsu City as a historical old city near Kyoto City, in the Japanese public long-term care insurance program to find the trend of the major patterns of the aging process for elderly people needing nursing care.

Differences in Monoamine Oxidase Activity in the Brain of Wistar and August Rats with High and Low Locomotor Activity: A Cytochemical Study.

PubMed

Sergutina, A V; Rakhmanova, V I

2016-06-01

Monoamine oxidase activity was quantitatively assessed by cytochemical method in brain structures (layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, hippocampal CA3 field) of rats of August line and Wistar population with high and low locomotor activity in the open fi eld test. Monoamine oxidase activity (substrate tryptamine) predominated in the nucleus accumbens of Wistar rats with high motor activity in comparison with rats with low locomotor activity. In August rats, enzyme activity (substrates tryptamine and serotonin) predominated in the hippocampus of animals with high motor activity. Comparison of August rats with low locomotor activity and Wistar rats with high motor activity (i.e. animals demonstrating maximum differences in motor function) revealed significantly higher activity of the enzyme (substrates tryptamine and serotonin) in the hippocampus of Wistar rats. The study demonstrates clear-cut morphochemical specificity of monoaminergic metabolism based on the differences in the cytochemical parameter "monoamine oxidase activity", in the studied brain structures, responsible for the formation and realization of goal-directed behavior in Wistar and August rats.

Voluntary physical exercise alters attentional orienting and social behavior in a rat model of attention-deficit/hyperactivity disorder.

PubMed

Hopkins, Michael E; Sharma, Mita; Evans, Gretchen C; Bucci, David J

2009-06-01

The effects of voluntary physical exercise on attentional function and social behavior were examined in male and female spontaneously hypertensive rats (SHR), a commonly used animal model of attention-deficit/hyperactivity disorder (ADHD). Rats in the exercise groups had free access to a running wheel for 2 weeks and then all rats received nonreinforced presentations of a visual stimulus (light) during the 1st training session, followed by daily sessions in which the light was paired with food. Nonexercising male and female SHR rats exhibited more unconditioned orienting behavior than Wistar-Kyoto rats. SHRs also exhibited impaired conditioning when the light was paired with food. Exercise reduced orienting in female SHRs but not in male SHRs. In the social interaction task, nonexercising male and female SHRs interacted more with an unfamiliar rat than Wistar-Kyoto rats. Exercise reduced the number of social interactions in female SHRs but not male SHRs. There were no differences in general locomotor activity observed between the nonexercising and exercising SHRs. These data indicate that exercise may preferentially benefit female SHRs, and has implications for using exercise as an intervention for ADHD and for understanding sex differences in the effects of exercise on behavior. Copyright (c) 2009 APA, all rights reserved.

Effect of renal denervation on dynamic autoregulation of renal blood flow.

PubMed

DiBona, Gerald F; Sawin, Linda L

2004-06-01

Vasoconstrictor intensities of renal sympathetic nerve stimulation elevate the renal arterial pressure threshold for steady-state stepwise autoregulation of renal blood flow. This study examined the tonic effect of basal renal sympathetic nerve activity on dynamic autoregulation of renal blood flow in rats with normal (Sprague-Dawley and Wistar-Kyoto) and increased levels of renal sympathetic nerve activity (congestive heart failure and spontaneously hypertensive rats). Steady-state values of arterial pressure and renal blood flow before and after acute renal denervation were subjected to transfer function analysis. Renal denervation increased basal renal blood flow in congestive heart failure (+35 +/- 3%) and spontaneously hypertensive rats (+21 +/- 3%) but not in Sprague-Dawley and Wistar-Kyoto rats. Renal denervation significantly decreased transfer function gain (i.e., improved autoregulation of renal blood flow) and increased coherence only in spontaneously hypertensive rats. Thus vasoconstrictor intensities of renal sympathetic nerve activity impaired the dynamic autoregulatory adjustments of the renal vasculature to oscillations in arterial pressure. Renal denervation increased renal blood flow variability in spontaneously hypertensive rats and congestive heart failure rats. The contribution of vasoconstrictor intensities of basal renal sympathetic nerve activity to limiting renal blood flow variability may be important in the stabilization of glomerular filtration rate.

Family expressiveness relates to happy emotion matching among 9-month-old infants.

PubMed

Ogren, Marissa; Burling, Joseph M; Johnson, Scott P

2018-06-07

Perceiving and understanding the emotions of those around us is an imperative skill to develop early in life. An infant's family environment provides most of their emotional exemplars in early development. However, the relation between the early development of emotion perception and family expressiveness remains understudied. To investigate this potential link to early emotion perception development, we examined 38 infants at 9 months of age. We assessed infants' ability to match emotions across facial and vocal modalities using an intermodal matching paradigm for angry-neutral, happy-neutral, and sad-neutral pairings. We also attained family expressiveness information via parent report. Our results indicate a significant positive relation between emotion matching and family expressiveness specific to the happy-neutral condition. However, we found no evidence for emotion matching for the infants as a group in any of the three conditions. These results suggest that family expressiveness does relate to emotion matching for the earliest developing emotional category among 9-month-old infants and that emotion matching with multiple emotions at this age is a challenging task. Copyright © 2018 Elsevier Inc. All rights reserved.

76 FR 5235 - Privacy Act of 1974, as Amended; Computer Matching Program (SSA Internal Match)-Match Number 1014

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-28

...; Computer Matching Program (SSA Internal Match)--Match Number 1014 AGENCY: Social Security Administration... regarding protections for such persons. The Privacy Act, as amended, regulates the use of computer matching....C. 552a, as amended, and the provisions of the Computer Matching and Privacy Protection Act of 1988...

Technical performance and match-to-match variation in elite football teams.

PubMed

Liu, Hongyou; Gómez, Miguel-Angel; Gonçalves, Bruno; Sampaio, Jaime

2016-01-01

Recent research suggests that match-to-match variation adds important information to performance descriptors in team sports, as it helps measure how players fine-tune their tactical behaviours and technical actions to the extreme dynamical environments. The current study aims to identify the differences in technical performance of players from strong and weak teams and to explore match-to-match variation of players' technical match performance. Performance data of all the 380 matches of season 2012-2013 in the Spanish First Division Professional Football League were analysed. Twenty-one performance-related match actions and events were chosen as variables in the analyses. Players' technical performance profiles were established by unifying count values of each action or event of each player per match into the same scale. Means of these count values of players from Top3 and Bottom3 teams were compared and plotted into radar charts. Coefficient of variation of each match action or event within a player was calculated to represent his match-to-match variation of technical performance. Differences in the variation of technical performances of players across different match contexts (team and opposition strength, match outcome and match location) were compared. All the comparisons were achieved by the magnitude-based inferences. Results showed that technical performances differed between players of strong and weak teams from different perspectives across different field positions. Furthermore, the variation of the players' technical performance is affected by the match context, with effects from team and opposition strength greater than effects from match location and match outcome.

Adolescent Atomoxetine Treatment in a Rodent Model of ADHD: Effects on Cocaine Self-Administration and Dopamine Transporters in Frontostriatal Regions

PubMed Central

Somkuwar, Sucharita S; Jordan, Chloe J; Kantak, Kathleen M; Dwoskin, Linda P

2013-01-01

Cocaine abuse and attention deficit/hyperactivity disorder (ADHD) are often comorbid. Preclinical research indicates that medial prefrontal (mPFC) and orbitofrontal (OFC) cortices are important neural substrates for both disorders. Using the spontaneously hypertensive rat (SHR) model of ADHD, we reported that adolescent treatment with the stimulant methylphenidate, a dopamine (DAT) and norepinephrine (NET) transporter inhibitor, enhanced cocaine self-administration during adulthood, and was associated with increased DAT function in mPFC. This study investigates the effects of atomoxetine ((R)-N-methyl-γ-(2-methylphenoxy)-benzenepropanamine hydrochloride) treatment, a selective NET inhibitor, during adolescence on cocaine self-administration and on DAT function and cell-surface expression in mPFC and OFC during adulthood. SHR acquired cocaine self-administration faster than Wistar–Kyoto and Wistar. Across cocaine doses, SHR earned more cocaine infusions and had higher progressive-ratio breakpoints than Wistar–Kyoto and Wistar, demonstrating that the SHR phenotype models comorbid ADHD and cocaine abuse. Prior atomoxetine treatment did not augment cocaine self-administration in SHR, but acquisition was enhanced in Wistar–Kyoto. No strain differences were found for DAT kinetic parameters or cellular localization in the vehicle controls. Atomoxetine did not alter DAT kinetic parameters or localization in SHR mPFC. Rather, atomoxetine decreased Vmax and DAT cell surface expression in SHR OFC, indicating that inhibition of NET by atomoxetine treatment during adolescence indirectly reduced DAT function and trafficking to the cell surface in OFC, specifically in the ADHD model. Thus, atomoxetine, unlike methylphenidate, does not enhance vulnerability to cocaine abuse in SHR and may represent an important alternative for teens with ADHD when drug addiction is a concern. PMID:23822950

Outcomes of Arthroscopic Rotator Cuff Repair in Patients Who Are 70 Years of Age or Older Versus Under 70 Years of Age: A Sex- and Tear Size-Matched Case-Control Study.

PubMed

Gwark, Ji-Yong; Sung, Chang-Meen; Na, Jae-Boem; Park, Hyung Bin

2018-05-19

To compare the structural and clinical outcomes after arthroscopic rotator cuff repair (ARCR) of a case group aged 70 and above with those of a control group younger than 70, with the 2 groups matched for sex and tear size. The case group, comprising 53 patients 70 or older, and the control group, comprising 159 patients younger than 70, all received ARCR to 1 shoulder with symptomatic full-thickness rotator cuff tear. The case and the control subjects, who were matched for sex and tear size to minimize bias related to tendon healing, received ARCR during the same period. The mean age was 71.8 ± 2.6 years in the case group and 59.3 ± 7.1 years in the control group. The minimum follow-up period was 1 year in both groups. Cuff integrity was evaluated using ultrasonography. Structural and clinical outcomes of the 2 groups were compared. Regarding structural outcomes, the complete healing, partial-thickness retear, and full-thickness retear rates were 66% (35/53), 15% (8/53), and 19% (10/53) in the case group, and 68% (108/159), 19% (30/159), and 13% (21/159), respectively, in the control group. The 2 groups had no significantly different retear rates (P = .52). Regarding clinical outcomes, the mean improvements in range of motion, pain, muscle strength, and age- and sex-matched Constant scores were not significantly different between the 2 groups (P > .37). The preoperative tear size was significantly associated with retear in both studied groups (P = .02). The clinical and structural outcomes of ARCR in patients 70 or older with symptomatic full-thickness rotator cuff tear are comparable with those in patients younger than 70 with at least 1-year follow-up. Preoperative tear size, a biological factor, is a strong predictor for retear. Level III, a retrospective comparative (case-control) study. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Patients with endometriosis have aneuploidy rates equivalent to their age-matched peers in the in vitro fertilization population.

PubMed

Juneau, Caroline; Kraus, Emily; Werner, Marie; Franasiak, Jason; Morin, Scott; Patounakis, George; Molinaro, Thomas; de Ziegler, Dominique; Scott, Richard T

2017-08-01

To determine whether endometriosis ultimately results in an increased risk of embryonic aneuploidy. Retrospective cohort. Infertility clinic. Patients participating in an in vitro fertilization (IVF) cycle from 2009-2015 using preimplantation genetic screening (PGS) who had endometriosis identified by surgical diagnosis or by ultrasound findings consistent with a persistent space-occupying disease whose sonographic appearance was consistent with endometriosis. None. Rate of aneuploidy in endometriosis patients undergoing IVF compared to controls without endometriosis undergoing IVF. There were 305 patients with endometriosis who produced 1,880 blastocysts that met the criteria for inclusion in the endometriosis group. The mean age of the patients with endometriosis was 36.1 ± 3.9 years. When the aneuploidy rates in patients with endometriosis and aneuploidy rates in patients without endometriosis were stratified by Society for Assisted Reproductive Technology age groups and compared, there were no statistically significant differences in the rate of aneuploidy (odds ratio 0.85; 95% confidence interval, 0.84-0.85). Patients with endometriosis undergoing IVF have aneuploidy rates equivalent to their age-matched peers in IVF population who do not have endometriosis. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Activation of adenosine receptors improves renal antioxidant status in diabetic Wistar but not SHR rats

PubMed Central

Patinha, Daniela; Afonso, Joana; Sousa, Teresa; Albino-Teixeira, António

2014-01-01

Background Diabetes and hypertension independently contribute to renal injury, and the major mechanisms involved are increased reactive oxygen species (ROS) bioavailability and renin-angiotensin system (RAS) activation. We investigated the role of adenosine in controlling ROS production and RAS activation associated with renal dysfunction in hypertension and diabetes. Methods Fourteen days after induction of diabetes with streptozotocin in 12-week-old male Wistar and spontaneously hypertensive (SHR) rats, animals were treated during 7 days with 2-chloroadenosine (CADO group, 5 mg/kg/d), a stable analogue of adenosine, or underwent a sham operation procedure. At the end of the study (day 21), intra-arterial systolic blood pressure (SBP) was measured, and 24-h urine and plasma samples and renal tissue were collected. Results CADO treatment decreased the plasma glucose concentration and glucose and protein excretion by more than 30% in both strains. CADO treatment decreased SBP in diabetic SHR rats (143 ± 8 versus 114 ± 4 mmHg, p < 0.05), but not in diabetic Wistar rats. The hypotensive effect of CADO was associated to a ∼70% increase in plasma angiotensinogen (AGT) concentration and a ∼50% decrease in urinary AGT excretion. CADO also caused a decrease in medullary and cortical hydrogen peroxide production of about 40%, which was associated with a proportional increase in glutathione peroxidase (GPx) activity in diabetic Wistar but not in diabetic SHR animals. Conclusions These results suggest that activation of adenosine receptors improves renal antioxidant capacity in diabetic Wistar but not SHR rats, although it improves glucose metabolism in both strains. Furthermore, activation of adenosine receptors does not seem to be directly influencing AGT production. PMID:24195577

Carbon-14 wiggle-match dating of peat deposits: advantages and limitations

NASA Astrophysics Data System (ADS)

Blaauw, Maarten; van Geel, Bas; Mauquoy, Dmitri; van der Plicht, Johannes

2004-02-01

Carbon-14 wiggle-match dating (WMD) of peat deposits uses the non-linear relationship between 14C age and calendar age to match the shape of a series of closely spaced peat 14C dates with the 14C calibration curve. The method of WMD is discussed, and its advantages and limitations are compared with calibration of individual dates. A numerical approach to WMD is introduced that makes it possible to assess the precision of WMD chronologies. During several intervals of the Holocene, the 14C calibration curve shows less pronounced fluctuations. We assess whether wiggle-matching is also a feasible strategy for these parts of the 14C calibration curve. High-precision chronologies, such as obtainable with WMD, are needed for studies of rapid climate changes and their possible causes during the Holocene. Copyright

45 CFR 98.63 - Allotments from the Matching Fund.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 98.63 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CHILD CARE AND DEVELOPMENT FUND Financial Management § 98.63 Allotments from the Matching Fund. (a) To each of the 50 States... of children under age 13 residing in the State bears to the national total of children under age 13...

45 CFR 98.63 - Allotments from the Matching Fund.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 98.63 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION CHILD CARE AND DEVELOPMENT FUND Financial Management § 98.63 Allotments from the Matching Fund. (a) To each of the 50 States... of children under age 13 residing in the State bears to the national total of children under age 13...

Site-specific activation of dopamine and serotonin transmission by aniracetam in the mesocorticolimbic pathway of rats.

PubMed

Nakamura, K; Shirane, M; Koshikawa, N

2001-04-06

The effects of aniracetam on extracellular levels of dopamine (DA), serotonin (5-HT) and their metabolites were examined in five brain regions in freely moving stroke-prone spontaneously hypertensive rats (SHRSP) using in vivo microdialysis. Basal DA release in SHRSP was uniformly lower in all regions tested than that in age-matched control Wistar Kyoto rats. 3,4-Dihydroxyphenylacetic acid and homovanillic acid levels were altered in the basolateral amygdala, dorsal hippocampus and prefrontal cortex of SHRSP. While basal 5-HT release decreased in the striatum and increased in the basolateral amygdala, there was no associated change in 5-hydroxyindoleacetic acid levels. Systemic administration of aniracetam to SHRSP enhanced both DA and 5-HT release with partly associated change in their metabolite levels in the prefrontal cortex, basolateral amygdala and dorsal hippocampus, but not in the striatum and nucleus accumbens shell, in a dose-dependent manner (30 and/or 100 mg/kg p.o.). Microinjection (1 and 10 ng) of aniracetam or its metabolites (N-anisoyl-GABA and 2-pyrrolidinone) into the nucleus accumbens shell produced no turning behavior. These findings indicate that SHRSP have a dopaminergic hypofunction throughout the brain and that aniracetam elicits a site-specific activation in mesocorticolimbic dopaminergic and serotonergic pathways in SHRSP, possibly via nicotinic acetylcholine receptors in the ventral tegmental area and raphe nuclei. The physiological roles in the aniracetam-sensitive brain regions may closely link with their clinical efficacy towards emotional disturbances appearing after cerebral infarction.

[Age-related aspects of male rats sexual behavior with different senescence rates].

PubMed

Amstislavskaia, T G; Gladkikh, D V; Belousova, I I; Maslova, L N; Kolosova, N G

2010-01-01

Social and sexual behavior of males Wistar and senescence-accelerated OXYS rats was studied. The experimental model excluding direct interaction between partners showed that the exploratory activity decreased with aging in rats of both strains, but social motivation didn't change. No interstrain differences in intensity of sexual motivation in the presence of an inaccessible receptive female were observed in 4-month rats. The level of sexual motivation of 12-month Wistar rats didn't differ from that of 4-month animals. However, in 12-month OXYS males, sexual motivation was decreased as compared to both 4- and 12-month Wistar rats. The same regularities were found under conditions of direct interaction with a partner. Behavioral changes in 12-month OXYS rats were considered as genetically determinate abnormality at the initial stage of sexual behavior, i.e., sexual motivation. The results suggest the accelerated senescence of the reproductive system of OXYS rats.

Racing performance of Standardbred trotting horses undergoing surgery of the carpal flexor sheath and age- and sex-matched control horses.

PubMed

Carmalt, James L; Johansson, Bengt C; Zetterström, Sandra M; McOnie, Rebecca C

2017-07-01

OBJECTIVE To determine factors affecting race speed in Swedish Standardbred horses undergoing surgery of the carpal flexor sheath (CFS), to investigate whether preoperative racing speed was associated with specific intraoperative findings and whether horses returned to racing, and to compare the performance of horses undergoing surgery of the CFS with that of age- and sex-matched control horses. ANIMALS 149 Swedish Standardbred trotters undergoing surgery of the CFS and 274 age- and sex-matched control horses. PROCEDURES Medical records of CFS horses were examined. Racing data for CFS and control horses were retrieved from official online records. Generalizing estimating equations were used to examine overall and presurgery racing speeds and the association of preoperative clinical and intraoperative findings with preoperative and postoperative speeds. Multivariable regression analysis was used to examine career earnings and number of career races. Kaplan-Meier survival analysis was used to compare career longevity between CFS and control horses. RESULTS CFS horses were significantly faster than control horses. The CFS horses that raced before surgery were slower as they approached the surgery date, but race speed increased after surgery. There were 124 of 137 (90.5%) CFS horses that raced after surgery. No intrathecal pathological findings were significantly associated with preoperative racing speed. Career longevity did not differ between CFS and control horses. CONCLUSIONS AND CLINICAL RELEVANCE Horses undergoing surgery of the CFS had a good prognosis to return to racing after surgery. Racing careers of horses undergoing surgery of the CFS were not significantly different from racing careers of control horses.

Intersensory Perception at Birth: Newborns Match Nonhuman Primate Faces and Voices

ERIC Educational Resources Information Center

Lewkowicz, David J.; Leo, Irene; Simion, Francesca

2010-01-01

Previous studies have shown that infants, including newborns, can match previously unseen and unheard human faces and vocalizations. More recently, it has been reported that infants as young as 4 months of age also can match the faces and vocalizations of other species raising the possibility that such broad multisensory perceptual tuning is…

Effectiveness of 7-valent pneumococcal conjugate vaccine in the prevention of invasive pneumococcal disease in children aged 7-59 months. A matched case-control study.

PubMed

Domínguez, Angela; Ciruela, Pilar; García-García, Juan José; Moraga, Fernando; de Sevilla, Mariona F; Selva, Laura; Coll, Francis; Muñoz-Almagro, Carmen; Planes, Ana María; Codina, Gemma; Jordán, Iolanda; Esteva, Cristina; Hernández, Sergi; Soldevila, Núria; Cardeñosa, Neus; Batalla, Joan; Salleras, Luis

2011-11-08

The aim of this study was to evaluate the effectiveness of the administration of the 7-valent pneumococcal conjugate vaccine in a region with an intermediate vaccination coverage. A matched case-control study was carried out in children aged 7-59 months with invasive pneumococcal disease (IPD) admitted to two university hospitals in Catalonia. Three controls matched for hospital, age, sex, date of hospitalization and underlying disease were selected for each case. Information on the vaccination status of cases and controls was obtained from the vaccination card, the child's health card, the hospital medical record or the vaccination register of the primary healthcare center where the child was attended for non-severe conditions. A conditional logistic regression analysis was made to control for the effect of possible confounding variables. The adjusted vaccination effectiveness of the complete vaccination schedule (3 doses at 2, 4 and 6 months and a fourth dose at 15 months, 2 doses at least two months apart in children aged 12-23 months or a single dose in children aged >24 months) in preventing IPD caused by vaccine serotypes was 93.7% (95% CI 51.8-99.2). It was not effective in preventing cases caused by non-vaccine serotypes. The results of this study carried out in a population with intermediate vaccination coverage confirm those of other observational studies showing high levels of effectiveness of routine 7-valent pneumococcal conjugate vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.

THE EFFECTS OF ATRAZINE METABOLITES ON PUBERTY IN THE MALE WISTAR RAT

EPA Science Inventory

The Effects of Atrazine Metabolites on Puberty in the Male Wistar Rat. D L Guidici, R L Cooper and T E Stoker. Endocrinology Branch, NHEERL, U.S. Environmental Protection Agency, RTP, NC.
Sponsor: R J Kavlock.
Atrazine (ATR), a chlorotriazine herbicide, alters pubertal pr...

PREFACE: Beyond Kyoto - the necessary road

NASA Astrophysics Data System (ADS)

Margrethe Basse, Ellen

2009-03-01

The Beyond Kyoto conference in Aarhus March 2009 was organised in collaboration with other knowledge institutions, businesses and authorities. It brought together leading scientists, policy-makers, authorities, intergovernmental organisations, NGO's, business stakeholders and business organisations. The conference was a joint interdisciplinary project involving many academic areas and disciplines. These conference proceedings are organised in central and recurring themes that cut across many debates on climate change, the climatic challenges as well as the solutions. In the front there is a short presentation of the conference concept. Part I of the proceedings focuses on issues related to the society - covering climate policy, law, market based instruments, financial structure, behaviour and consumption, public participation, media communication and response from indigenous peoples etc. Part II of the proceedings concerns the scientific knowledge base on climate related issues - covering climate change processes per se, the potential impacts of projected climate change on biodiversity and adaptation possibilities, the interplay between climate, agriculture and biodiversity, emissions, agricultural systems, increasing pressure on the functioning of agriculture and natural areas, vulnerability to extreme weather events and risks in respect to sea-level rise etc. The conference proceedings committee consists of four professors from Aarhus University: Jens-Christian Svenning, Jørgen E Olesen, Mads Forchhammer and Ellen Margrethe Basse. Aarhus University's Climate Secretariat has had the overall responsibility for coordinating the many presentations, as well as the practical side of arranging the conference and supporting the publication of papers. As Head of the Climate Secretariat and Chair of Aarhus University's Climate Panel, I would like to thank everyone for their contribution. This applies both to the scientific and the practical efforts. Special thanks to

Dietary intake of ain-93 standard diet induces Fatty liver with altered hepatic fatty acid profile in Wistar rats.

PubMed

Farias Santos, Juliana; Suruagy Amaral, Monique; Lima Oliveira, Suzana; Porto Barbosa, Júnia; Rego Cabral, Cyro; Sofia Melo, Ingrid; Bezerra Bueno, Nassib; Duarte Freitas, Johnatan; Goulart Sant'ana, Antônio; Rocha Ataíde, Terezinha

2015-05-01

There are several standard diets for animals used in scientific research, usually conceived by scientific institutions. The AIN-93 diet is widely used, but there are some reports of fatty liver in Wistar rats fed this diet. We aimed to evaluate the hepatic repercussions of the AIN-93 diet intake in Wistar rats. Forty newly-weaned 21-day-old male Wistar rats were fed either the AIN-93 diet or a commercial diet for either 1 month or 4 months. Weight gain, serum biochemistry, hepatic histology, and hepatic fatty acid profile were analyzed. Hepatic steatosis was observed, especially in the group fed the AIN-93 diet. Serum blood glucose, absolute and relative liver weight and hepatic levels of oleic, palmitoleic, stearic, and palmitic fatty acids were related to the observed steatosis, while lipidogram and serum markers of liver function and injury were not. AIN-93 diet induced acute hepatic steatosis in Wistar rats, which may compromise its use as a standard diet for experimental studies with rodents. The hepatic fatty acid profile was associated with steatosis, with possible implications for disease prognosis. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Comorbidity is more common and occurs earlier in persons living with HIV than in HIV-uninfected matched controls, aged 50 years and older: A cross-sectional study.

PubMed

Maciel, Rafael Aguiar; Klück, Helena Moreira; Durand, Madeleine; Sprinz, Eduardo

2018-05-01

At present, data are limited on the comorbidity profiles associated with aging people with HIV in the developing world, where most such people live. The aim of this study was to compare the disease burden between older HIV-positive subjects and HIV-negative matched controls in Brazil. This was a cross-sectional analysis of the South Brazilian HIV Cohort. Individuals aged 50 years and older were enrolled at Hospital de Clínicas de Porto Alegre and matched with HIV-negative controls from the primary practice unit of the same hospital. Multimorbidity (the presence of two or more comorbid conditions) and the number of non-infectious comorbidities were compared. Poisson regression was used to identify factors associated with multimorbidity. A total of 208 HIV-positive subjects were matched to 208 HIV-negative controls. Overall, the median age was 57 years and 56% were male. The prevalence of multimorbidity was higher in HIV-positive subjects than in HIV-negative controls (63% vs. 43%, p<0.001), and the median number of comorbidities was 2, compared to 1 in controls (p<0.001). The duration of HIV infection (p=0.02) and time on treatment in years (p=0.015) were associated with greater multimorbidity in HIV-positive persons. In this large cohort from the developing world, multimorbidity was found to be more common in HIV-positive subjects than in HIV-negative controls. The duration of HIV and time on antiretrovirals were associated with multimorbidity. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Whey proteins protect more than red meat against azoxymethane induced ACF in Wistar rats.

PubMed

Belobrajdic, D P; McIntosh, G H; Owens, J A

2003-07-30

Protein type and density have been shown to influence colon cancer risk using a carcinogen-induced rat model. It is suggested that red meat may promote colon cancer risk more than whey proteins. The aim of this study was to evaluate the influence of red meat, whey protein and their density in the diet on the number of aberrant crypt foci (ACF), preneoplastic markers in Wistar rats. The sources of protein, red meat as barbecued kangaroo muscle meat, and whey protein concentrate were fed to rats to provide 8, 16 and 32% protein by weight in a modified AIN-93 diet with low fiber, low calcium and high polyunsaturated fat. Adult Wistar rats (13 weeks of age) were fed these diets for 4 weeks and then two s.c. injections of azoxymethane, 15 mg/kg BW, were administered 1 week apart. Diets were fed for a further 8 weeks, rats were then killed, their colons fixed in formalin saline and stained with methylene blue to quantify ACF number. Fecal samples were collected and the fecal water was isolated for quantification of heme and thiobarbituric acid reactive substances. Increasing red meat density correlated positively, while increasing dairy protein density correlated negatively with rate of weight gain (p<0.05). Dietary intake was not significantly affected by protein type or density. The 32% whey protein group had significantly less ACF in the proximal colon in comparison to the 16 and 32% red meat groups (p<0.05). This reduction in ACF number in the whey protein group may be caused by hormones associated with the reduction in weight gain, and/or by components of whey protein concentrate such as cysteine, lactose and conjugated linoleic acid which have been shown to have anti-cancer effects. Using ACF number as an index, whey protein appeared to be more protective than red meat.

High reliability solid refractive index matching materials for field installable connections in FTTH network

NASA Astrophysics Data System (ADS)

Saito, Kotaro; Kihara, Mitsuru; Shimizu, Tomoya; Yoneda, Keisuke; Kurashima, Toshio

2015-06-01

We performed environmental and accelerated aging tests to ensure the long-term reliability of solid type refractive index matching material at a splice point. Stable optical characteristics were confirmed in environmental tests based on an IEC standard. In an accelerated aging test at 140 °C, which is very much higher than the specification test temperature, the index matching material itself and spliced fibers passing through it had steady optical characteristics. Then we performed an accelerated aging test on an index matching material attached to a built-in fiber before splicing it in the worst condition, which is different from the normal use configuration. As a result, we confirmed that the repeated insertion and removal of fiber for splicing resulted in failure. We consider that the repetition of adhesion between index matching material and fibers causes the splice to degrade. With this result, we used the Arrhenius model to estimate a median lifetime of about 68 years in a high temperature environment of 60 °C. Thus solid type index matching material at a splice point is highly reliable over long periods under normal conditions of use.

A post-Kyoto partner: Considering the Montreal Protocol as a tool to manage nitrous oxide

NASA Astrophysics Data System (ADS)

Mauzerall, D. L.; Kanter, D.; Ravishankara, A. R.; Daniel, J. S.; Portmann, R. W.; Grabiel, P.; Moomaw, W.; Galloway, J. N.

2012-12-01

While nitrous oxide (N2O) was recently identified as the largest remaining anthropogenic threat to the stratospheric ozone layer, it is currently regulated under the 1997 Kyoto Protocol due to its simultaneous ability to warm the climate. The threat N2O poses to the stratospheric ozone layer, coupled with the uncertain future of the international climate regime, motivates our exploration of issues that could be relevant to the Parties to the 1987 Montreal Protocol if they decide to take measures to manage N2O in the future. There are clear legal avenues for the Montreal Protocol and its parent treaty, the 1985 Vienna Convention, to regulate N2O, as well as several ways to share authority with the existing and future international climate treaties. N2O mitigation strategies exist to address its most significant anthropogenic sources, including agriculture, where behavioral practices and new technologies could contribute significantly to mitigation efforts. Existing policies managing N2O and other forms of reactive nitrogen could be harnessed and built upon by the Montreal Protocol's existing bodies to implement N2O controls. Given the tight coupling of the nitrogen cycle, such controls would likely simultaneously reduce emissions of reactive nitrogen and hence have co-benefits for ecosystems and public health. Nevertheless, there are at least three major regulatory challenges that are unique and central to N2O control: food security, equity, and the nitrogen cascade. The possible inclusion of N2O in the Montreal Protocol need not be viewed as a sign of the Kyoto Protocol's failure to adequately deal with climate change, given the complexity of the issue. Rather, it could represent an additional tool in the field of sustainable development diplomacy.lt;img border=0 src="images/B43K-06_B.jpg">

Matching motivation enhancement treatment to client motivation: re-examining the Project MATCH motivation matching hypothesis.

PubMed

Witkiewitz, Katie; Hartzler, Bryan; Donovan, Dennis

2010-08-01

The current study was designed to re-examine the motivation matching hypothesis from Project MATCH using growth mixture modeling, an analytical technique that models variation in individual drinking patterns. Secondary data analyses of data from Project MATCH (n = 1726), a large multi-site alcoholism treatment-matching study. Percentage of drinking days was the primary outcome measure, assessed from 1 month to 12 months following treatment. Treatment assignment, alcohol dependence symptoms and baseline percentage of drinking days were included as covariates. The results provided support for the motivation matching hypothesis in the out-patient sample and among females in the aftercare sample: the majority of individuals with lower baseline motivation had better outcomes if assigned to motivation enhancement treatment (MET) compared to those assigned to cognitive behavioral treatment (CBT). In the aftercare sample there was a moderating effect of gender and alcohol dependence severity, whereby males with lower baseline motivation and greater alcohol dependence drank more frequently if assigned to MET compared to those assigned to CBT. Results from the current study lend partial support to the motivation-matching hypothesis and also demonstrated the importance of moderating influences on treatment matching effectiveness. Based upon these findings, individuals with low baseline motivation in out-patient settings and males with low levels of alcohol dependence or females in aftercare settings may benefit more from motivational enhancement techniques than from cognitive-behavioral techniques.

Acute and subchronic toxicological evaluation of Mequindox in Wistar rats.

PubMed

Ihsan, Awais; Wang, Xu; Huang, Xian-ju; Liu, Yu; Liu, Qin; Zhou, Wen; Yuan, Zong-hui

2010-01-01

We studied an acute and subchronic oral toxicity of Mequindox (MEQ), a quinoxaline 1,4-dioxide antimicrobial promoter, in Wistar rats according to OECD guidelines. For acute toxicity study, single doses of MEQ at 175, 550 and 2000 mg/kg b.w. were administered to rats by oral gavage. The calculated LD(50) was 550 mg/kg b.w. In subchronic study, rats were fed diets containing 0, 55, 110 or 275 mg MEQ/kg. There was a reduction in body weight of rats fed 275 mg MEQ/kg diet. At 90 days autopsy, a significant decrease in the kidney weight was observed in males while an increase in relative liver and adrenal weights were observed in females fed 275 mg MEQ/kg diet. There was a significant increased in alanineaminotransferase (ALT) and malondialdehyde (MDA) concentrations in males, superoxide dismutase (SOD) activities in females, and aspartateaminotransferase (AST) levels in serum of both genders fed 275 mg MEQ/kg diet. Other toxic effects of 275 mg MEQ/kg diet included significant decrease in sodium and significant increase in potassium concentrations in serum in both genders. We may conclude that MEQ can induce hepatic and adrenal histological changes as well as leaking of different serum constituents in Wistar rats. Copyright 2010 Elsevier Inc. All rights reserved.

The Promotion of Peace Education through Guides in Peace Museums. A Case Study of the Kyoto Museum for World Peace, Ritsumeikan University

ERIC Educational Resources Information Center

Tanigawa, Yoshiko

2015-01-01

This paper focuses on how peace education at a peace museum is promoted by a volunteer guide service for visitors. Peace museums are places where many materials related to war and peace history are on display. To support the learning experience of museum visitors, many peace museums in Japan provide a volunteer guide service. The Kyoto Museum for…

Matched comparison of primary versus salvage laparoscopic pyeloplasty.

PubMed

Ambani, Sapan N; Yang, David Y; Wolf, J Stuart

2017-06-01

To compare our experience with salvage laparoscopic pyeloplasty, using a matched control set of primary laparoscopic pyeloplasty patients. We retrospectively reviewed patients who underwent laparoscopic pyeloplasty from 1996 to 2014 by a single surgeon. At least 12 months of follow-up was required. Salvage patients were matched 1:3 with primary patients. Matching was based on age ±5 years, body mass index (BMI) ±5, and type of pyeloplasty (dismembered vs. non-dismembered). Primary outcome was failure as defined as re-intervention following laparoscopic pyeloplasty (does not include temporary stenting without definitive retreatment). Of 128 laparoscopic pyeloplasty procedures, ten were salvage. These patients were matched to 26 patients who underwent a primary laparoscopic pyeloplasty in a 1:3 manner. One salvage pyeloplasty failed to match due to BMI, and the closest matches were made. Four salvage patients had one overlapping match, reducing the primary group to 26 patients. There were no differences in pre-, intra-, and postoperative variables between groups, except for operative time (salvage 247 min, primary 175 min, p = 0.03). With similar duration of radiologic and symptomatic follow-up, there was no significant difference in the rate of freedom from intervention. When matching for factors that could affect success, salvage laparoscopic pyeloplasty performed as well as primary pyeloplasty except for a longer operative time. In experienced hands, salvage laparoscopic pyeloplasty for ureteropelvic junction obstruction recurrence after prior pyeloplasty is a safe and effective procedure, and should be considered an excellent alternative to the more commonly recommended endopyelotomy.

Modelling relationships between match events and match outcome in elite football.

PubMed

Liu, Hongyou; Hopkins, Will G; Gómez, Miguel-Angel

2016-08-01

Identifying match events that are related to match outcome is an important task in football match analysis. Here we have used generalised mixed linear modelling to determine relationships of 16 football match events and 1 contextual variable (game location: home/away) with the match outcome. Statistics of 320 close matches (goal difference ≤ 2) of season 2012-2013 in the Spanish First Division Professional Football League were analysed. Relationships were evaluated with magnitude-based inferences and were expressed as extra matches won or lost per 10 close matches for an increase of two within-team or between-team standard deviations (SD) of the match event (representing effects of changes in team values from match to match and of differences between average team values, respectively). There was a moderate positive within-team effect from shots on target (3.4 extra wins per 10 matches; 99% confidence limits ±1.0), and a small positive within-team effect from total shots (1.7 extra wins; ±1.0). Effects of most other match events were related to ball possession, which had a small negative within-team effect (1.2 extra losses; ±1.0) but a small positive between-team effect (1.7 extra wins; ±1.4). Game location showed a small positive within-team effect (1.9 extra wins; ±0.9). In analyses of nine combinations of team and opposition end-of-season rank (classified as high, medium, low), almost all between-team effects were unclear, while within-team effects varied depending on the strength of team and opposition. Some of these findings will be useful to coaches and performance analysts when planning training sessions and match tactics.

Endoscopic detection rate of sessile serrated lesions in Lynch syndrome patients is comparable with an age- and gender-matched control population: case-control study with expert pathology review.

PubMed

Vleugels, Jasper L A; Sahin, Husna; Hazewinkel, Yark; Koens, Lianne; van den Berg, Jose G; van Leerdam, Monique E; Dekker, Evelien

2018-05-01

Carcinogenesis in Lynch syndrome involves fast progression of adenomas to colorectal cancer (CRC) because of microsatellite instability. The role of sessile serrated lesions (SSLs) and the serrated neoplasia pathway in these patients is unknown. The aim of this matched case-control study was to compare endoscopic detection rates and distribution of SSLs in Lynch syndrome patients with a matched control population. We collected data of Lynch syndrome patients with a proven germline mutation who underwent colonoscopy between January 2011 and April 2016 in 2 tertiary referral hospitals. Control subjects undergoing elective colonoscopy from 2011 and onward for symptoms or surveillance were selected from a prospectively collected database. Patients were matched 1:1 for age, gender, and index versus surveillance colonoscopy. An expert pathology review of serrated polyps was performed. The primary outcomes included the detection rates and distribution of SSLs. We identified 321 patients with Lynch syndrome who underwent at least 1 colonoscopy. Of these, 223 Lynch syndrome patients (mean age, 49.3; 59% women; index colonoscopy, 56%) were matched to 223 control subjects. SSLs were detected in 7.6% (95% confidence interval, 4.8-11.9) of colonoscopies performed in Lynch syndrome patients and in 6.7% (95% confidence interval, 4.1-10.8) of control subjects (P = .86). None of the detected SSLs in Lynch syndrome patients contained dysplasia. The detection rate of SSLs in Lynch syndrome patients undergoing colonoscopy is comparable with a matched population. These findings suggest that the role of the serrated neoplasia pathway in CRC development in Lynch syndrome seems to be comparable with that in the general population. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Pulmonary Tuberculosis Is Associated With Biomass Fuel Use Among Rural Women in Pakistan: An Age- and Residence-Matched Case-Control Study.

PubMed

Rabbani, Unaib; Sahito, Ambreen; Nafees, Asaad Ahmed; Kazi, Ambreen; Fatmi, Zafar

2017-04-01

Facility-based, age- and residential area-matched case-control study was conducted in Sindh, Pakistan to determine association between biomass fuel use for cooking and pulmonary tuberculosis (TB). Cases were women with pulmonary TB, and controls were those suffering from other diseases. Current users of biomass fuel were at higher risk of pulmonary TB (adjusted matched odds ratio [mOR] = 3.0; 95% CI = 1.1-4.9) compared with nonusers. In comparison with former biomass users (women not using biomass for >10 years), recent biomass users (women who switched from biomass to nonbiomass ≤10 years ago), and current (lifetime) users were at a higher risk in a dose-response manner (adjusted mOR = 2.8, 95% CI = 0.9-8.2 and adjusted mOR = 3.9, 95% CI = 1.4-10.7, respectively). Population attributable fraction for TB related to biomass fuel use was 40.6% (95% CI = 35.5%-45.7%). This study strengthens the evidence that biomass fuel use for cooking is associated with pulmonary TB and risk increases with duration of exposure.

Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Xin-Ai; Jia, Lin-Lin; Cui, Wei

We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4 weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heartmore » weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-κB p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-α in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-κB p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN

Energy demands during a judo match and recovery.

PubMed