bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of parasympathetic reactivation after exercise
Authors: Goldberger Jeffrey J. , Le Francis Kiet , Lahiri Marc , Kannankeril Prince J. , Ng Jason , Kadish Alan H.
Published: January 2006

The objective of this study was to evaluate whether heart rate variability (HRV) can be used as an index of parasympathetic reactivation after exercise. Heart rate recovery after exercise has recently been shown to have prognostic significance and has been postulated to be related to abnormal recovery of parasympathetic tone. Ten normal subjects [5 men and 5 women; age 33 ± 5 yr (mean ± SE)] exercised to their maximum capacity, and 12 subjects (10 men and 2 women; age 61 ± 10 yr) with coronary artery disease exercised for 16 min on two separate occasions, once in the absence of atropine and once with atropine (0.04 mg/kg) administered during exercise. The root mean square residual (RMS), which measures the deviation of the R-R intervals from a straight line, as well as the standard deviation (SD) and the root mean square successive difference of the R-R intervals (MSSD), were measured on successive 15-, 30-, and 60-s segments of a 5-min ECG obtained immediately after exercise. In recovery, the R-R interval was shorter with atropine ( P < 0.0001). Without atropine, HRV, as measured by the MSSD and RMS, increased early in recovery from 4.1 ± 0.4 and 3.7 ± 0.4 ms in the first 15 s to 7.2 ± 1.0 and 7.4 ± 0.9 ms after 1 min, respectively ( P < 0.0001). RMS (range 1.7–2.1 ms) and MSSD were less with atropine ( P < 0.0001). RMS remained flat throughout recovery, whereas MSSD showed some decline over time from 3.0 to 2.2 ms ( P < 0.002). RMS and MSSD were both directly related ( r2 = 0.47 and 0.56, respectively; P < 0.0001) to parasympathetic effect, defined as the difference in R-R interval without and with atropine. In conclusion, RMS and MSSD are parameters of HRV that can be used in the postexercise recovery period as indexes of parasympathetic reactivation after exercise. These tools may improve our understanding of parasympathetic reactivation after exercise and the prognostic significance of heart rate recovery.
Chronic angiotensin-(1–7) prevents cardiac fibrosis in DOCA-salt model of hypertension
Authors: Grobe Justin L. , Mecca Adam P. , Mao Haoyu , Katovich Michael J.
Published: January 2006

Cardiac remodeling is a hallmark hypertension-induced pathophysiology. In the current study, the role of the angiotensin-(1–7) fragment in modulating cardiac remodeling was examined. Sprague-Dawley rats underwent uninephrectomy surgery and were implanted with a deoxycorticosterone acetate (DOCA) pellet. DOCA animals had their drinking water replaced with 0.9% saline solution. A subgroup of DOCA-salt animals was implanted with osmotic minipumps, which delivered angiotensin-(1–7) chronically (100 ng·kg−1·min−1). Control animals underwent sham surgery and were maintained on normal drinking water. Blood pressure was measured weekly with the use of the tail-cuff method, and after 4 wk of treatment, blood pressure responses to graded doses of angiotensin II were determined by direct carotid artery cannulation. Ventricle size was measured, and cross sections of the heart ventricles were paraffin embedded and stained using Masson's Trichrome to measure interstitial and perivascular collagen deposition and myocyte diameter. DOCA-salt treatment caused significant increases in blood pressure, cardiac hypertrophy, and myocardial and perivascular fibrosis. Angiotensin-(1–7) infusion prevented the collagen deposition effects without any effect on blood pressure or cardiac hypertrophy. These results indicate that angiotensin-(1–7) selectively prevents cardiac fibrosis independent of blood pressure or cardiac hypertrophy in the DOCA-salt model of hypertension.
Inverse regulation of preproendothelin-1 and endothelin-converting enzyme-1β genes in cardiac cells by mechanical load
Authors: Pikkarainen Sampsa , Tokola Heikki , Kerkelä Risto , Ilves Mika , Mäkinen Markus , Orzechowski Hans-Dieter , Paul Martin , Vuolteenaho Olli , Ruskoaho Heikki
Published: January 2006

Mechanical stretch and para- and/or autocrine factors, including endothelin-1, induce hypertrophy of cardiac myocytes and proliferation of fibroblasts. To investigate the effect of mechanical load on endothelin-1 production and endothelin system gene expression in neonatal rat ventricular myocytes and fibroblasts, we exposed cells to cyclic mechanical stretch in vitro (0.5 Hz, 10–25% elongation, from 1 min to 24 h). Endothelin-1 peptide levels were measured from culture media of myocytes and fibroblasts and human umbilical vein endothelial cells (positive control) by specific radioimmunoassay. Preproendothelin-1 promoter activity was measured via transfection of reporter plasmids and mRNA levels with Northern blot analysis or quantitative RT-PCR. Activity of extracellular signal-regulated kinase was quantified with specific kinase assay. We found that stretching of myocytes activated preproendothelin-1 gene expression, including promoter activation, transient mRNA level increases, and augmented endothelin-1 secretion. In contrast, preproendothelin-1 gene expression was inhibited in stretched fibroblasts. Endothelin-converting enzyme-1β mRNA levels elevated in stretched fibroblasts but decreased in stretched myocytes. Endothelin receptor type A mRNA levels declined in stretched myocytes, whereas levels were below detection in fibroblasts. Stretch activated extracellular signal-regulated kinase in myocytes, and when the kinase activity was pharmacologically inhibited, the preproendothelin-1 induction was suppressed. Transient overexpression of mitogen-activated ERK-activating kinase-1 induced preproendothelin-1 promoter in myocytes. In summary, mechanical stretch distinctly regulates endothelin system gene expression in cardiac myocytes and fibroblasts. The inhibition of the endothelin system may affect cardiac mechanotransduction and therefore provides an approach in treatment of load-induced cardiac pathology.
Renal mitochondrial dysfunction in spontaneously hypertensive rats is attenuated by losartan but not by amlodipine
Authors: de Cavanagh Elena M. V. , Toblli Jorge E. , Ferder León , Piotrkowski Bárbara , Stella Inés , Inserra Felipe
Published: January 2006

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 H2O2production 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 α-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.
Orexin neuron-mediated skeletal muscle vasodilation and shift of baroreflex during defense response in mice
Authors: Zhang Wei , Sakurai Takeshi , Fukuda Yasuichiro , Kuwaki Tomoyuki
Published: January 2006

We have previously shown that some features of the defense response, such as increases in arterial blood pressure (AP), heart rate (HR), and ventilation were attenuated in prepro-orexin knockout (ORX-KO) mice. Here, we examined whether the same was true in orexin neuron-ablated [orexin/ataxin-3 transgenic mice (ORX/ATX-Tg)] mice. In addition, we examined other features of the defense response: skeletal muscular vasodilation and shift of baroreceptor reflex. In both anesthetized and conscious conditions, basal AP in ORX/ATX-Tg mice was significantly lower by ∼20 mmHg than in wild-type (WT) controls, as was the case in ORX-KO mice. The difference in AP disappeared after treatment with an α-blocker but not with a β-blocker, indicating lower sympathetic vasoconstrictor outflow. Stimulation of the perifornical area (PFA) in urethane-anesthetized ORX/ATX-Tg mice elicited smaller and shorter-lasting increases in AP, HR, and ventilation, and skeletal muscle vasodilation than in WT controls. In addition, air jet stress-induced elevations of AP and HR were attenuated in conscious ORX/ATX-Tg mice. After pretreatment with a β-blocker, atenolol, stimulation of PFA suppressed phenylephrine (50 μg/kg iv)-induced bradycardia (ΔHR = −360 ± 29 beats/min without PFA stimulation vs. −166 ± 26 during stimulation) in WT. This demonstrated the resetting of the baroreflex. In ORX/ATX-Tg mice, however, no significant suppression was observed (−355 ± 16 without stimulation vs. −300 ± 30 during stimulation). The present study provided further support for our hypothesis that orexin-containing neurons in PFA play a role as a master switch to activate multiple efferent pathways of the defense response and also operate as a regulator of basal AP.
Kupffer cell-generated PGE2triggers the febrile response of guinea pigs to intravenously injected LPS
Authors: Li Zhonghua , Perlik Vit , Feleder Carlos , Tang Ying , Blatteis Clark M.
Published: January 2006

Because the onset of fever induced by intravenously (iv) injected bacterial endotoxic lipopolysaccharides (LPS) precedes the appearance in the bloodstream of pyrogenic cytokines, the presumptive peripheral triggers of the febrile response, we have postulated previously that, in their stead, PGE2could be the peripheral fever trigger because it appears in blood coincidentally with the initial body core temperature (Tc) rise. To test this hypothesis, we injected Salmonella enteritidis LPS (2 μg/kg body wt iv) into conscious guinea pigs and measured their plasma levels of LPS, PGE2, TNF-α, IL-1β, and IL-6 before and 15, 30, 60, 90, and 120 min after LPS administration; Tcwas monitored continuously. The animals were untreated or Kupffer cell (KC) depleted; the essential involvement of KCs in LPS fever was shown previously. LPS very promptly (<10 min) induced a rise of Tcthat was temporally correlated with the elevation of plasma PGE2. KC depletion prevented the Tcand plasma PGE2rises and slowed the clearance of LPS from the blood. TNF-α was not detectable in plasma until 30 min and in IL-1β and IL-6 until 60 min after LPS injection. KC depletion did not alter the times of appearance or magnitudes of rises of these cytokines, except TNF-α, the maximal level of which was increased approximately twofold in the KC-depleted animals. In a follow-up experiment, PGE2antiserum administered iv 10 min before LPS significantly attenuated the febrile response to LPS. Together, these results support the view that, in guinea pigs, PGE2rather than pyrogenic cytokines is generated by KCs in immediate response to iv LPS and triggers the febrile response.
Perinatal photoperiod organizes adult immune responses in Siberian hamsters (Phodopus sungorus)
Authors: Weil Zachary M. , Pyter Leah M. , Martin Lynn B. , Nelson Randy J.
Published: January 2006

Individuals of many nontropical rodent species display reproductive, immunological, and somatic responses to day length. In general, short day (SD) lengths inhibit reproduction and enhance immune function in the laboratory when all other conditions are held constant. Most studies to date have focused on seasonal variation in immune function in adulthood. However, perinatal photoperiods also communicate critical day length information and serve to establish a developmental trajectory appropriate for the time of year. Nontropical rodents born early in the breeding season undergo rapid reproductive development, presumably to promote mating success during their first reproductive season. Rodents born late in the breeding season suspend somatic growth and puberty until the following vernal breeding season. We tested the hypothesis that perinatal day lengths have similar enduring effects on the immune system of rodents. Siberian hamsters ( Phodopus sungorus) were maintained prenatally and until weaning (21 days) in either SDs (8 h light:16 h dark) or long days (LD) (16 h light:8 h dark), then they were weaned into either the opposite photoperiod or maintained in their natal photoperiod, forming four groups (LD-LD, LD-SD, SD-LD, and SD-SD). After 8-wk in these conditions, cell-mediated immune activity was compared among groups. SD-SD hamsters of both sexes enhanced immune function relative to all other groups. The reproductive effects of perinatal photoperiod were not evident by the end of the experiment; circulating testosterone and cortisol sampled at the end of the experiment reflected the postweaning, but not the perinatal photoperiod. This experiment demonstrates long-lasting organizational effects of perinatal photoperiod on the rodent immune system and indicates that photoperiod-induced changes in the immune system are dissociable from changes in the reproductive system.
Ventilatory response to hyperoxia in newborn mice heterozygous for the transcription factorPhox2b
Authors: Ramanantsoa N. , Vaubourg V. , Dauger S. , Matrot B. , Vardon G. , Chettouh Z. , Gaultier C. , Goridis C. , Gallego J.
Published: January 2006

Heterozygous mutations of the transcription factor PHOX2B have been found in most patients with central congenital hypoventilation syndrome, a rare disease characterized by sleep-related hypoventilation and impaired chemosensitivity to sustained hypercapnia and sustained hypoxia. PHOX2B is a master regulator of autonomic reflex pathways, including peripheral chemosensitive pathways. In the present study, we used hyperoxic tests to assess the strength of the peripheral chemoreceptor tonic drive in Phox2b+/− newborn mice. We exposed 69 wild-type and 67 mutant mice to two hyperoxic tests (12-min air followed by 3-min 100% O2) 2 days after birth. Breathing variables were measured noninvasively using whole body flow plethysmography. The initial minute ventilation decrease was larger in mutant pups than in wild-type pups: −37% (SD 13) and −25% (SD 18), respectively, P < 0.0001. Furthermore, minute ventilation remained depressed throughout O2exposure in mutants, possibly because of their previously reported impaired CO2chemosensitivity, whereas it returned rapidly to the normoxic level in wild-type pups. Hyperoxia considerably increased total apnea duration in mutant compared with wild-type pups ( P = 0.0001). A complementary experiment established that body temperature was not influenced by hyperoxia in either genotype group and, therefore, did not account for genotype-related differences in the hyperoxic ventilatory response. Thus partial loss of Phox2b function by heterozygosity did not diminish the tonic drive from peripheral chemoreceptors.
Comparison of early and late responses to antigen of sensitized guinea pig parenchymal lung strips
Authors: Lanças Tatiana , Kasahara David I. , Prado Carla M. , Tibério Iolanda F. L. C. , Martins Milton A. , Dolhnikoff Marisa
Published: January 2006

The peripheral lung parenchyma has been studied as a component of the asthmatic inflammatory response. During induced constriction, tissue resistance increases in different asthma models. Approximately 60% of the asthmatic patients show early and late responses. The late response is characterized by more severe airway obstruction. In the present study, we evaluated lung parenchymal strips mechanics in ovalbumin-sensitized guinea pigs, trying to reproduce both early and late inflammatory responses. Oscillatory mechanics of lung strips were performed in a control group (C), in an early response group (ER), and in two late response groups: 17 h (L1) and 72 h (L2) after the last ovalbumin challenge. Measurements of resistance and elastance were obtained before and after ovalbumin challenge in C and ER groups and before and after acetylcholine challenge in all groups. Using morphometry, we assessed the density of eosinophils and smooth muscle cells, as well as collagen and elastin content in lung strips. The baseline and postagonist values of resistance and elastance were increased in ER, L1, and L2 groups compared with C ( P ≤ 0.001). The morphometric analysis showed an increase in alveolar eosinophil density in ER and L2 groups compared with C ( P < 0.05). There was a significant correlation between eosinophil density in parenchymal strips of C, L1, and L2 groups and values of resistance and elastance postacetylcholine ( r = 0.71, P = 0.001 and r = 0.74, P < 0.001, respectively). The results show that the lung parenchyma is involved in the late response, and the constriction response in this phase is related to the eosinophilic inflammation.
Diaphyseal bone formation in murine tibiae in response to knee loading
Authors: Zhang Ping , Tanaka Shigeo M. , Jiang Hui , Su Min , Yokota Hiroki
Published: January 2006

Mechanical stimulation is critical for bone architecture and bone mass. The aim of this study was to examine the effects of mechanical loads applied to the knee. The specific question was whether loads applied to the tibial epiphysis would enhance bone formation in the tibial diaphysis. In C57/BL/6 mice, loads of 0.5 N were applied for 3 min per day for 3 days at 5, 10, or 15 Hz. Bone samples were harvested 13 days after the last loading. The strains were measured 13 ± 2 μstrains at 5 Hz in the diaphysis. The histomorphometric data in the diaphysis clearly showed enhanced bone formation. First, compared with nonloaded control the cross-sectional cortical area was increased by 11% at 5 Hz and 8% at 10 Hz (both P < 0.05). Second, the cortical thickness was elevated by 12% at 5 Hz ( P < 0.01) and 8% at 10 Hz ( P < 0.05). Third, mineralizing surface (MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS) were increased at 5 Hz ( P < 0.01 for MS/BS; P < 0.001 for MAR and BFR/BS) and at 10 Hz ( P < 0.05 for MS/BS; P < 0.01 for MAR and BFR/BS). Bone formation was enhanced more extensively in the medial side than the lateral or the posterior side. The results reveal that knee loading is an effective means to enhance bone formation in the tibial diaphysis in a loading-frequency dependent manner without inducing significant in situ strain at the site of bone formation.
α-Adrenergic receptor-mediated restraint of skeletal muscle blood flow during prolonged exercise
Authors: DeLorey Darren S. , Hamann Jason J. , Kluess Heidi A. , Clifford Philip S. , Buckwalter John B.
Published: January 2006

Sympathetic nervous system restraint of skeletal muscle blood flow during dynamic exercise has been well documented. However, whether sympathetic restraint of muscle blood flow persists and is constant throughout prolonged exercise has not been established. We hypothesized that both α1- and α2-adrenergic receptors would restrain skeletal muscle blood flow throughout prolonged constant-load exercise and that the restraint would increase as a function of exercise duration. Mongrel dogs were instrumented chronically with transit-time flow probes on the external iliac arteries and an indwelling catheter in a branch of the femoral artery. Flow-adjusted doses of selective α1- (prazosin) and α2-adrenergic receptor (rauwolscine) antagonists were infused after 5, 30, and 50 min of treadmill exercise at 3 and 6 miles/h. During mild-intensity exercise (3 miles/h), prazosin infusion resulted in a greater ( P < 0.05) increase in vascular conductance (VC) after 5 [42% (SD 6)], compared with 30 [28% (SD 6)] and 50 [28% (SD 8)] min of running. In contrast, prazosin resulted in a similar increase in VC after 5 [29% (SD 10)], 30 [24% (SD 9)], and 50 [22% (SD 9)] min of moderate-intensity (6 miles/h) exercise. Rauwolscine infusion resulted in a greater ( P < 0.05) increase in VC after 5 [39% (SD 14)] compared with 30 [26% (SD 9)] and 50 [22% (SD 4)] min of exercise at 3 miles/h. Rauwolscine infusion produced a similar increase in VC after 5 [19% (SD 3)], 30 [15% (SD 6)], and 50 [16% (SD 2)] min of exercise at 6 miles/h. These results suggest that the ability of α1- and α2-adrenergic receptors to produce vasoconstriction and restrain blood flow to active muscles may be influenced by both the intensity and duration of exercise.
Contribution of thermal and nonthermal factors to the regulation of body temperature in humans
Authors: Mekjavic Igor B. , Eiken Ola
Published: January 2006

The set point has been used to define the regulated level of body temperature, suggesting that displacements of core temperature from the set point initiate heat production (HP) and heat loss (HL) responses. Human and animal experiments have demonstrated that the responses of sweating and shivering do not coincide at a set point but rather establish a thermoeffector threshold zone. Neurophysiological studies have demonstrated that the sensor-to-effector pathways for HP and HL overlap and, in fact, mutually inhibit each other. This reciprocal inhibition theory, presumably reflecting the manner in which thermal factors contribute to homeothermy in humans, does not incorporate the effect of nonthermal factors on temperature regulation. The present review examines the actions of these nonthermal factors within the context of neuronal models of temperature regulation, suggesting that examination of these factors may provide further insights into the nature of temperature regulation. It is concluded that, although there is no evidence to doubt the existence of the HP and HL pathways reciprocally inhibiting one another, it appears that such a mechanism is of little consequence when comparing the effects of nonthermal factors on the thermoregulatory system, since most of these factors seem to exert their influence in the region after the reciprocal cross-inhibition. At any given moment, both thermal and several nonthermal factors will be acting on the thermoregulatory system. It may, therefore, not be appropriate to dismiss the contribution of either when discussing the regulation of body temperature in humans.
Sex-based effects on the distribution of NK cell subsets in response to exercise and carbohydrate intake in adolescents
Authors: Timmons Brian W. , Tarnopolsky Mark A. , Bar-Or Oded
Published: January 2006

Carbohydrate (CHO) supplementation and female sex independently influence the natural killer (NK) cell response to acute exercise. Consequently, this study sought to elucidate sex-based differences in the distribution of NK cell subsets (i.e., CD56dimand CD56bright) in response to exercise and CHO intake. Twenty-two healthy 14-yr-old girls ( n = 11) and boys ( n = 11) cycled for 60 min at 70% maximal oxygen consumption while drinking 6% CHO (CT) or flavored water (WT). Blood was collected at rest, during exercise (30 and 60 min), and during recovery (30 and 60 min) to identify CD3−CD56dimand CD3−CD56brightNK cells. The activation marker CD69 was also determined on CD3−CD56+cells. CD56dimresponses, expressed as proportions or cell counts, were greater ( P ≤ 0.01) in girls by 67 and 105%, respectively. CD56brightcell counts ( P = 0.006), but not CD56brightproportions ( P = 0.89), were greater in girls by 82%. Both CD56dimand CD56brightsubset responses, expressed as proportions or cell counts, were lower ( P ≤ 0.01) in CT vs. WT by 33–36%. The CD56bright-to-CD56dimratio decreased at 30 min of exercise but increased during recovery ( P < 0.001), with no effect of sex or CHO. Regardless of trial, CD3−CD56+cells expressed ∼18% higher levels of CD69 during recovery in girls but not boys ( P = 0.03), despite similar proportions and counts of CD69+cells. These results demonstrate sex-based differences in the distribution of NK cell subsets and activation status in response to exercise, but not CHO intake, and further support the need to control for sex in exercise immunology studies.
Human ventilatory responsiveness to hypoxia is unrelated to maximal aerobic capacity
Authors: Sheel A. William , Koehle Michael S. , Guenette Jordan A. , Foster Glen E. , Sporer Benjamin C. , Diep Tu T. , McKenzie Donald C.
Published: January 2006

Ventilatory responsiveness to hypoxia (HVR) has been reported to be different between highly trained endurance athletes and healthy sedentary controls. However, a linkage between aerobic capacity and HVR has not been a universal finding. The purpose of this study was to examine the relationship between HVR and maximal oxygen consumption (V̇o2 max) in healthy men with a wide range of aerobic capacities. Subjects performed a HVR test followed by an incremental cycle test to exhaustion. Participants were classified according to their maximal aerobic capacity. Those with a V̇o2 max of ≥60 ml·kg−1·min−1 were considered highly trained ( n = 13); those with a V̇o2 max of 50–60 ml·kg−1·min−1 were considered moderately-trained ( n = 18); and those with a V̇o2 max of <50 ml·kg−1·min−1 were considered untrained ( n = 24). No statistical differences were detected between the three groups for HVR ( P > 0.05), and the HVR values were variable within each group (range: untrained = 0.28–1.61, moderately trained = 0.23–2.39, and highly trained = 0.08–1.73 l·min·%arterial O2 saturation−1). The relationship between HVR and V̇o2 max was not statistically significant ( r = −0.1723; P > 0.05). HVR was also unrelated to maximal minute ventilation and ventilatory equivalents for O2 and CO2. We found that a spectrum of hypoxic ventilatory control is present in well-trained endurance athletes and moderately and untrained men. We interpret these observations to mean that other factors are more important in determining hypoxic ventilatory control than physical conditioning per se.
Frequency-dependent contractile response of isolated cardiac trabeculae under hypo-, normo-, and hyperthermic conditions
Authors: Hiranandani Nitisha , Varian Kenneth D. , Monasky Michelle M. , Janssen Paul M. L.
Published: January 2006

The body is from time to time exposed to nonnormothermic conditions; both hypo- and hyperthermia can occur as a result of external (environment) or internal (pathogens, allergens) stressors. To preserve life under hypo- and hyperthermic conditions, adequate perfusion of vital organs is mandated. Although cardiac output regulation under hyperthermic conditions has been studied, the mechanical response of basic contractile function of the myocardium itself is incompletely understood. Accordingly, we set out to test mechanical output of isolated myocardium under hyperthermic conditions and to compare the results with the hypo- and normothermic response in the same tissue. We observed that, in absence of a frequency change, developed force decreased markedly. At a physiological normal stimulation rate of 6 Hz, developed force decreases to 67.2 ± 2.6% at 42°C compared with 37°C. In addition, twitch timing characteristics also accelerate, allowing for a faster relaxation; time from peak tension to 50% relaxation is ∼23% faster (from 31.4 ± 2.6 to 24.4 ± 1.7 ms). Although this faster relaxation in turn prevents a steep increase in diastolic tension at high frequencies, the very fast calcium kinetics now prevent a more complete activation of the myofilaments, resulting in a lower twitch-force maximum at hyperthermic conditions. Even at maximal β-adrenergic stimulation, developed force is well below levels reached at physiological temperature.
Sex difference in cardiomyocyte function in normal and metallothionein transgenic mice: the effect of diabetes mellitus
Authors: Ceylan-Isik Asli F. , LaCour Karissa H. , Ren Jun
Published: January 2006

Evidence suggests a sex difference in intrinsic physiological and diabetic myocardial contractile function related to antioxidant properties of female ovarian hormones. This study was designed to examine the effect of cardiac overexpression of antioxidant metallothionein on intrinsic and diabetic cardiomyocyte function. Weight-matched wild-type (FVB) and metallothionein transgenic mice of both sexes were made diabetic with streptozotocin (220 mg/kg). Contractile and intracellular Ca2+ properties were evaluated including peak shortening (PS), time to PS, time to 90% relengthening (TR90), maximal velocity of shortening or relengthening (±d L/d t), fura-2 fluorescence intensity change, and Ca2+ decay rate. Akt and transcription factor c-Jun levels were evaluated by Western blot. Myocytes from female FVB mice exhibited lower PS, ±d L/d t, and fura-2 fluorescence intensity change, prolonged time to PS, TR90, and Ca2+ decay compared with male FVB mice. Interestingly, this sex difference was not present in metallothionein mice. Diabetes depressed PS, ±d L/d t and caffeine-induced Ca2+ release, as well as prolonged TR90 and Ca2+ decay in male FVB mice, whereas it only reduced PS in female FVB mice. These diabetic dysfunctions were nullified by metallothionein in both sexes. Females displayed elevated Akt phosphorylation and reduced c-Jun phosphorylation. Diabetes dampened Akt phosphorylation in male FVB mice and enhanced c-Jun in both sexes. Diabetes-induced alterations in Akt phosphorylation and c-Jun were abolished by metallothionein. The sex difference in Akt phosphorylation but not c-Jun levels was reversed by metallothionein. These data indicate that antioxidant capacity plays an important role in sex differences in both intrinsic and diabetic cardiomyocyte contractile properties possibly related to phosphorylation of Akt and c-Jun.
Denervation effects on myonuclear domain size of rat diaphragm fibers
Authors: Aravamudan Bharathi , Mantilla Carlos B. , Zhan Wen-Zhi , Sieck Gary C.
Published: January 2006

Denervation (DNV) of rat diaphragm muscle (DIAm) leads to selective atrophy of type IIx and IIb fibers, whereas the cross-sectional area of type I and IIa fibers remains unchanged or slightly hypertrophied. DIAm DNV also increases satellite cell mitotic activity and myonuclear apoptosis. Similar to other skeletal muscles, DIAm fibers are multinucleated, and each myonucleus regulates the gene products in a finite fiber volume, i.e., myonuclear domain (MND). MND size varies across DIAm fiber types in rank order, I < IIa < IIx < IIb [fiber type based on myosin heavy chain isoform expression]. We hypothesized that, after DNV, the total number of myonuclei per fiber does not change and, accordingly, that MND changes proportionately to the change in fiber size regardless of fiber type. Adult rats underwent unilateral (right side) DIAm DNV, and after 2 wk single fibers were dissected. Fiber cross-sectional area, myonuclear number, and MND were measured by confocal microscopy, and these values in DNV DIAm were compared with those obtained in controls. After DNV, type I fibers hypertrophied, type IIa fiber size was unchanged, and type IIx and IIb fibers atrophied compared with control. The total number of myonuclei per fiber was not affected by DNV. Accordingly, after DNV, type I fiber MND increased by 25%, whereas it decreased in type IIx and IIb fibers by 50 and 70%, respectively. These results suggest that MND is not maintained after DNV-induced DIAm fiber hypertrophy or atrophy. These results are interpreted with respect to consequent effects of DNV on myonuclear transcriptional activity and protein turnover.
Differential effects of strength training leading to failure versus not to failure on hormonal responses, strength, and muscle power gains
Authors: Izquierdo Mikel , Ibañez Javier , González-Badillo Juan José , Häkkinen Keijo , Ratamess Nicholas A. , Kraemer William J. , French Duncan N. , Eslava Jesus , Altadill Aritz , Asiain Xabier , Gorostiaga Esteban M.
Published: January 2006

The purpose of this study was to examine the efficacy of 11 wk of resistance training to failure vs. nonfailure, followed by an identical 5-wk peaking period of maximal strength and power training for both groups as well as to examine the underlying physiological changes in basal circulating anabolic and catabolic hormones. Forty-two physically active men were matched and then randomly assigned to either a training to failure (RF; n = 14), nonfailure (NRF; n = 15), or control groups (C; n = 13). Muscular and power testing and blood draws to determine basal hormonal concentrations were conducted before the initiation of training (T0), after 6 wk of training (T1), after 11 wk of training (T2), and after 16 wk of training (T3). Both RF and NRF resulted in similar gains in 1-repetition maximum bench press (23 and 23%) and parallel squat (22 and 23%), muscle power output of the arm (27 and 28%) and leg extensor muscles (26 and 29%), and maximal number of repetitions performed during parallel squat (66 and 69%). RF group experienced larger gains in the maximal number of repetitions performed during the bench press. The peaking phase (T2 to T3) after NRF resulted in larger gains in muscle power output of the lower extremities, whereas after RF it resulted in larger gains in the maximal number of repetitions performed during the bench press. Strength training leading to RF resulted in reductions in resting concentrations of IGF-1 and elevations in IGFBP-3, whereas NRF resulted in reduced resting cortisol concentrations and an elevation in resting serum total testosterone concentration. This investigation demonstrated a potential beneficial stimulus of NRF for improving strength and power, especially during the subsequent peaking training period, whereas performing sets to failure resulted in greater gains in local muscular endurance. Elevation in IGFBP-3 after resistance training may have been compensatory to accommodate the reduction in IGF-1 to preserve IGF availability.
Prediction Equation of Resting Energy Expenditure in an Adult Spanish Population of Obese Adult Population
Authors: de Luis D.A. , Aller R. , Izaola O. , Romero E.
Published: January 2006

Objective: The aim of our study was to evaluate the accuracy of the equations to estimate REE in obese patents and develop a new equation in our obese population. Subjects and Methods: A population of 200 obesity outpatients was analyzed in a prospective way. The following variables were specifically recorded: age, weight, body mass index (BMI), waist circumference, and waist-to-hip ratio. Basal glucose, insulin, and TSH (thyroid-stimulating hormone) were measured. An indirect calorimetry and a tetrapolar electrical bioimpedance were performed. REE measured by indirect calorimetry was compared with REE obtained by prediction equations to obese or nonobese patients. Results: The mean age was 44.8 ± 16.81 years and the mean BMI 34.4 ± 5.3. Indirect calorimetry showed that, as compared to women, men had higher resting energy expenditure (REE) (1,998.1 ± 432 vs. 1,663.9 ± 349 kcal/day; p < 0.05) and oxygen consumption (284.6 ± 67.7 vs. 238.6 ± 54.3 ml/min; p < 0.05). Correlation analysis among REE obtained by indirect calorimetry and REE predicted by prediction equations showed the next data; Berstein’s equation (r = 0.65; p < 0.05), Harris Benedict’s equation (r = 0.58; p < 0.05), Owen’s equation (r = 0.56; p < 0.05), Ireton’s equation (r = 0.58; p < 0.05) and WHO’s equation (r = 0.57; p < 0.05). Both the Berstein’s and the Ireton’s equations overpredicted REE and showed nonsignificant mean differences form measured REE. The Owen’s, WHO’s, and Harris Benedict’s equations underpredicted REE. Our male prediction equation was REE = 58.6 + (6.1×weight (kg)) + (1,023.7×height (m)) – (9.5×age). The female model was REE = 1,272.5 + (9.8×weight (kg)) – (61.6×height (m)) – (8.2×age). Our prediction equations showed a nonsignificant difference with REE measured (–3.7 kcal/day) with a significant correlation coefficient (r = 0.67; p < 0.05). Conclusion: Previously developed prediction equations overestimated and underestimated REE measured. WHO equation developed in normal weight individuals provided the closest values. The two new equations (male and female equations) developed in our study had a good accuracy.
Hand Strike-Induced Hemolysis and Adaptations in Iron Metabolism in Basque Ball Players
Authors: Córdova Martínez Alfredo , Villa Gerardo , Aguiló Antoni , Tur Josep A. , Pons Antoni
Published: January 2006

Introduction: Basque ball players (BBPs) make repeated hand strikes to the ball which involves continuous mechanical trauma. Objective: The aim of this work is to describe the hematological variations and changes in iron metabolism occurring in BBPs as a result of acute and continuous practice of this special sport native to Northern Spain. Methods: 40 healthy male subjects volunteered to participate in this study: 11 subjects who exercise moderately (control group) but do not play Basque ball sport and 29 professional BBPs were studied in two situations: before a match (BM group) and after a match (AM group). The following hematological parameters were determined: red blood cell count (RBC), hemoglobin and hematocrit; MCV, MCH and MCHC. The following variables were measured in serum: iron, ferritin, transferrin, transferrin saturation, proteins, and lactate dehydrogenase (LDH). Proteins and hemoglobin were determined in urine. Results: The BM group showed lower hematocrit, MCV, hemoglobin and serum transferrin levels, and higher LDH than controls. The AM group showed higher RBC, hemoglobin, serum proteins, iron, transferrin and LDH levels, lower plasma volume, and higher urine hemoglobin and protein levels than the BM group. Conclusions: Basque ball playing induces hemolysis and increases the plasma capability to quench free iron, but its clinical consequences on iron metabolism do not seem to be enough to take an iron intake proportional to the caloric intake. In order to prevent, in the long term, the development of anemia in these peculiar sportsmen, it would be useful that medical teams observe urine blood losses and oxidative stress in these BBPs.
Prevention of Colorectal Cancer in Inflammatory Bowel Disease: Value of Screening and 5-Aminosalicylates
Authors: Munkholm Pia , Loftus Jr. Edward V. , Reinacher-Schick Anke , Kornbluth Asher , Mittmann Ulrich , Esendal Burak
Published: January 2006

Colorectal cancer is a serious complication of inflammatory bowel disease. Given this fact, it is necessary to examine the opportunities for current and future approaches to colorectal cancer prevention. The value of surveillance colonoscopy and chemoprevention of colorectal cancer with 5′-aminosalicylic acid has been evaluated in the recent literature. The current state of knowledge in the epidemiology of and new approaches to the prevention of cancer and dysplasia in inflammatory bowel disease were reviewed. It is concluded that there is significant preclinical and clinical evidence to suggest that 5-aminosalicylate drugs reduce the risk of colorectal neoplasia. However, the minimal dosage to achieve this chemopreventive effect remains unclear. There is also indirect evidence to suggest that surveillance colonoscopy is beneficial for patients with inflammatory bowel disease, particularly in those with long-standing pancolitis or primary sclerosing cholangitis-associated inflammatory bowel disease. However, definitive proof from prospective clinical trials is not available.
Variation of Host Cell Tropism of Porcine Endogenous Retroviruses Expressed in Chinese Banna Minipig Inbred
Authors: Li Zhang , Ping Yu , Shengfu Li , Yangzhi Zeng , Jingqiu Cheng , Youping Li , Hong Bu
Published: January 2006

A serious donor-organ shortage urges the use of animal donors to treat a wide appropriate variety of major health problems including organ failure and diabetes. However, the promise of clinical xenotransplantation is offset at the present time by the potential of a public health risk due to the cross-species transmission of pathogens from animal donors to human patients. In particular, the transmission of porcine endogenous retrovirus (PERV) is a major concern. In this study, cell tropism of PERV was tested by in vitro infection of human primary cells and cell lines. Coculture of PERV supernatant derived from PK15 with human primary cells and cell lines resulted in the transfer and expression of PERV-specific sequences and the establishment of a productive infection. In the detection of tropism variation of PERV in pigs, 293 cells were cocultured with mitogenic-activated and lethally irradiated PBMC from 12 Banna minipig inbred (BMI). The results were that six coculture groups were PERV-positive. However, infectious virus was not detected when activated PBMC from the other 7 pigs were cocultivated with human cells known to be permissive for PERV, which indicated a tropism variation among the tested individuals. All these findings demonstrate that the presence of endogenous viruses in source animals needs to be carefully considered when the infectious disease potential of xenotransplantation is being assessed.
Galanin Fiber Hypertrophy within the Cholinergic Nucleus Basalis during the Progression of Alzheimer’s Disease
Authors: Counts Scott E. , Chen Er-Yun , Che Shaoli , Ikonomovic Milos D. , Wuu Joanne , Ginsberg Stephen D. , DeKosky Steven T. , Mufson Elliott J.
Published: January 2006

Galanin (GAL)-containing fibers enlarge and hyperinnervate remaining cholinergic basal forebrain (CBF) neurons within the anterior nucleus basalis (NB) in late-stage Alzheimer’s disease (AD). Whether GAL hypertrophy occurs in the CBF in the prodromal or early stages of AD remains unknown. The present study used GAL immunohistochemistry and an unbiased semiquantitative scoring method to evaluate GAL innervation in the anterior NB of subjects clinically diagnosed as having no cognitive impairment, mild cognitive impairment or early-stage (mild/moderate) AD. There was no difference in GAL fiber staining within the anterior NB across the three clinical groups examined. Furthermore, GAL fiber innervation was not correlated with the number of NB neurons expressing the nerve growth factor receptors p75NTR or TrkA or with cortical choline acetyltransferase activity in the same cases. Single-cell gene expression analysis demonstrated that cholinergic NB neurons express mRNA for the GAL receptors GALR1, GALR2 and GALR3, yet the levels of these mRNAs were unchanged across the three diagnostic groups. These observations indicate that GAL hypertrophy within the anterior NB subfield is a late-stage AD response, which may play a role in regulating the cholinergic tone of remaining basocortical projection neurons.
New Insight into Abnormal Muscle Vasodilatory Responses in Aged Hypertensive Rats by in vivo Nuclear Magnetic Resonance Imaging of Perfusion
Authors: Bertoldi Didier , Parzy Elodie , Fromes Yves , Wary Claire , Leroy-Willig Anne , Carlier Pierre G.
Published: January 2006

Objective: Increased peripheral arterial resistances and decreased maximum vasodilation are characteristic features of chronic hypertension. However, little data are available in the literature regarding the possible alterations in the temporal patterns of vasodilatory responses elicited by various stimuli. Design: This question was addressed by measuring skeletal muscle perfusion using nuclear magnetic resonance imaging combined with arterial spin labeling. Methods: Ninety-week-old male spontaneously hypertensive (SHR; n = 7) and normotensive Wistar Kyoto (WKY; n = 8) rats were studied, and calf muscle perfusion was measured at rest and during reactive hyperemia following total ischemia of 5 and 30 min duration. Results: Reactive hyperemia profiles differed according to duration of ischemia. In WKY rats, 5 min of ischemia induced a short peak of hyperemia lasting no more than 63 s, while 30 min of ischemia were followed by a prolonged hyperemic response of 261 s. In SHRs, after 5 min of ischemia, peak muscle arterial conductance was decreased to 0.5 ± 0.3 versus 0.9 ± 0.3 ml·min–1·100 g–1·mm Hg–1 in the WKY rats (p < 0.05), as expected. After 30 min of ischemia, there was, in addition, a shortening of the hyperemic response duration. Time to post-ischemic half normalization of arterial conductance was 38 ± 24 s in the SHRs versus 149 ± 58 s in the WKY rats (p < 0.001). Conclusion: In vivo perfusion measurement not only confirmed the existence of a reduced maximum peripheral vasodilation in chronically hypertensive rats, it revealed a blunted hyperemic response after prolonged ischemia in the SHRs, which might be an important contributing factor to the increased sensitivity to ischemia in hypertension.
Homocysteine-Induced Endothelin-1 Release Is Dependent on Hyperglycaemia and Reactive Oxygen Species Production in Bovine Aortic Endothelial Cells
Authors: Sethi Amarjit S. , Lees Delphine M. , Douthwaite Julie A. , Dawnay Anne B. , Corder Roger
Published: January 2006

Background: Elevated plasma homocysteine (Hcy) is a risk factor for coronary disease. The objective of this study was to investigate whether Hcy either alone or in high glucose conditions induces endothelin-1 (ET-1) synthesis via the production of reactive oxygen species (ROS). Methods: Bovine aortic endothelial cells were grown in high (25 mmol/l) and low (5 mmol/l) glucose medium. Results: In high glucose, Hcy caused a time-dependent increase in ET-1 release, which was greatest with 50 µmol/l Hcy at 24 h (p < 0.01). This effect was not seen in low glucose conditions. In high glucose and 50 µmol/l Hcy, ET-1 mRNA levels were maximal after 1 h (p < 0.05). Tissue factor mRNA levels were raised at 4 h (p < 0.05) and functional activity was raised at 6 h (p < 0.01). Intracellular ROS production was increased by 50 µmol/l Hcy after 24 h (p < 0.05) but only in high glucose. To investigate the role of mitochondrial metabolism in ROS production, cells were incubated with thenoyltrifluoroacetone (inhibitor of complex II) or carbonyl cyanide m-chlorophenylhydrazone (uncoupler of oxidative phosphorylation). Both compounds abolished the Hcy-induced increase in ROS production and ET-1 release. There was an alteration in intracellular glutathione (GSH) levels with Hcy treatment with more oxidised GSH present. Conclusion: The combined metabolic burden of Hcy and high glucose stimulates ET-1 synthesis in bovine aortic endothelial cells via a mechanism dependent on the production of mitochondrial ROS, but may not be generalisable to all types of endothelial cells.