bluuebunny/crossref_metadata_2025 huggingface dataset:
Production de radicaux superoxydes par radiolyse pulsée de l'eau à transfert d'énergie linéique (TEL) élevé
Authors: Baldacchino G , Trupin-Wasselin V , Bouffard S , Balanzat E , Gardès-Albert M , Abedinzadeh Z , Jore D , Deycard S , Hickel B
Published: April 2011

The radiolysis of water with heavy ions of high linear energy transfer (LET) (-dE/dx) is characterized, in deaerated medium, by the production of superoxide anions, the radiolytic yields of which increase with the LET. Radiobiological interest in such radical species comes from the oxidative stress which may be generated by their dismutation in O2 and H2O2 in anoxic medium (radiotherapy with heavy ions). A brief review of the measurements of superoxide free radicals in aqueous solution by indirect or direct methods is presented. Moreover, some experimental results obtained by pulse radiolysis with Ar18+ ions (TEL = 290 keV·µm-1), are described. The interpretation of the kinetics takes into account the superoxide absorbance and that of hydrogen peroxide, which is present at the millisecond time scale.Key words: pulse radiolysis, heavy ions, superoxide radicals, high LET, kinetics.[Traduit par la Rédaction]
Avian somatotrophs: differentiation, morphology, distribution, and regulation
Authors: Hull K L , Murphy A , Harvey S
Published: April 2011

Growth hormone (GH) is primarily synthesized, stored, and released by pituitary somatotrophs. These cells comprise a highly labile population that continuously undergoes proliferation, differentiation, and morphogenesis in response to changing physiological stimuli. They are also functionally and morphologically heterogeneous with distinct spatial and temporal distribution within the pituitary gland. The characteristics of these cells are discussed in this brief review.Key words: somatotroph, aves, growth hormone, adenohypophysis.
Pituitary and extrapituitary growth hormone: Pit-1 dependence?
Authors: Harvey S , Azumaya Y , Hull K L
Published: April 2011

Growth hormone (GH) is primarily produced in pituitary somatotrophs. The synthesis of this hormone is thought to be dependent upon a pituitary-specific transcription factor (Pit-1). However, many extrapituitary tissues are now known to express GH genes. The extrapituitary production of GH may therefore indicate an extrapituitary distribution of the Pit-1 gene. The extrapituitary production of GH may, alternatively, indicate that GH expression occurs independently of Pit-1 in extrapituitary tissues. These possibilities are considered in this brief review.Key words: growth hormone, pituitary, pituitary transcription factor 1.
Effect of transient stretch on intracellular Ca2+during triggered propagated contractions in intact trabeculae
Authors: Miura Masahito , Wakayama Yuji , Sugai Yoshinao , Kagaya Yutaka , Watanabe Jun , ter Keurs Henk EDJ , Shirato Kunio
Published: April 2011

Transient stretch of cardiac muscle during a twitch contraction may dissociate Ca2+from myofilaments into the cytosol at the moment of quick release of the muscle. We studied the effect of stretch and quick release of trabeculae on changes in intracellular Ca2+([Ca2+]i) during triggered propagated contractions (TPCs). Trabeculae were dissected from the right ventricle of 9 rat hearts. [Ca2+]iwas measured using electrophoretically injected fura-2. Force was measured using a silicon strain gauge and sarcomere length was measured using laser diffraction techniques. Reproducible TPCs (n = 13) were induced by trains of electrical stimuli (378 ± 19 ms interval) for 7.5 s at [Ca2+]oof 2.0 mM (27.9 ± 0.2°C). The latency of the TPC force and the underlying increase in [Ca2+]iwas calculated from the time (TimeF) between the last stimulus and the peak of TPC force (PeakF), or the time (TimeCa) between the last stimulus and the peak of the increase in [Ca2+]iduring the TPCs (PeakCa). As a result of a 10% increase in muscle length for 150-200 ms during the last stimulated twitches, TimeFand TimeCadecreased and PeakFand PeakCaincreased significantly (n = 13). In addition, transient stretch sometimes induced a twitch contraction subsequent to the accelerated TPC and its underlying increase in [Ca2+]i. These results suggest that Ca2+binding and dissociation from the myofilaments by the stretch and quick release of muscle may modulate the TPC force and the underlying increases in [Ca2+]iand play an important role in the induction of arrhythmias.Key words: rat cardiac trabeculae, stretch, calcium transients.
Therapeutic potential of dietary phase 2 enzyme inducers in ameliorating diseases that have an underlying inflammatory component
Authors: Juurlink Bernhard HJ
Published: April 2011

Many diseases associated with ageing have an underlying oxidative stress and accompanying inflammatory component, for example, Alzheimer's disease or atherosclerosis. Reviewed in this manuscript are: the role of oxidative stress in activating the transcription factor nuclear factor kappa B (NFκB), the role of NFκB in activating pro-inflammatory gene transcription, strong oxidants produced by cells, anti-oxidant defense systems, the central role of phase 2 enzymes in the anti-oxidant defense, dietary phase 2 enzyme inducers and evidence that dietary phase 2 enzymes decrease oxidative stress. It is likely that a diet containing phase 2 enzyme inducers may ameliorate or even prevent diseases that have a prominent inflammatory component to them. Research should be directed into the potential therapeutic effects of dietary phase 2 enzyme inducers in ameliorating diseases with an underlying oxidative stress and inflammatory component to them.Key words: Alzheimer's disease, atherosclerosis, diet, glutathione, inflammation, stroke.
The effects of α-lactabumin and whey protein concentrate on dry matter recovery, TCA soluble protein levels, and peptide distribution in the rat gastrointestinal tract
Authors: Pantako Odile T , Lemieux Lise , Amiot Jean
Published: April 2011

The effects of two dietary proteins on dry matter recovery, trichloroacetic acid (TCA) soluble protein concentration, and peptide distribution in gastrointestinal contents were investigated in rats trained to consume, in a single 2-hour daily meal, diets containing α-lactalbumin (α-LA) or whey protein concentrate (WPC) for two weeks. Compared with the WPC diet, the α-LA diet emptied faster from the stomach. Dry matter recovery was higher in the stomach contents of rats fed the WPC diet than in those given the α-LA diet, but dry matter content in the small intestine was comparable. TCA soluble protein levels in the stomach and the small intestinal contents were also significantly (P < 0.001) higher in rats fed the WPC diet. The concentration of peptides having molecular weights (MW) ranging from 12 50030 000 daltons (Da) was higher in the stomach contents of rats fed the WPC diet. Conversely, the level of peptides ranging from 500012 500 Da was higher in the stomach contents of rats fed the α-LA diet. For both diets, the small intestinal contents were characterized by high levels of amino acids and small peptides. These results suggest that the hydrolysis and absorption of α-LA is faster than that of WPC.Key words: In vivo protein digestion, peptides absorption, whey protein concentrate, α-lactalbumin, stomach emptying.
Effect of exogenous growth hormone on somatic growth, gonadal development, and hepatic CYP2C11 and CYP2C12 expression in prepubertal intact male rats
Authors: Kawai Masahiko , Bandiera Stelvio M , Chang Thomas KH , Bellward Gail D
Published: April 2011

The influence of exogenous growth hormone (GH) on pubertal maturation, as assessed by growth, age of preputial separation, testicular development, and hepatic expression of sexually dimorphic cytochrome P450 (CYP) enzymes, was investigated. Treatment of 22-day old prepubertal intact male rats with twice daily subcutaneous (sc) injections of rat recombinant GH (0.12 µg/g body weight) for 12 or 21 days did not affect body weight, skeletal growth, or testicular weight. By comparison, GH suppressed hepatic CYP2C11 enzyme activity, protein, and mRNA levels but induced CYP2C12 expression. GH suppressed CYP2C11 expression by approximately 60% in prepubertal rats as compared with 30% in adult rats, whereas it increased CYP2C12 levels to 80% of the normal female levels but had no effect in adult male rats. Twice daily intravenous injections of GH suppressed CYP2C11 only. Increasing the sc dose of GH 30-fold produced little or no additional change in CYP2C11 or CYP2C12 expression, whereas it modestly increased body weight and skeletal growth and reduced testicular weight. Overall, the present study provides the first demonstration that prepubertal administration (22-33 days of age) of GH at a pharmacologically relevant dose (0.12 µg/g twice daily) suppressed hepatic expression of CYP2C11 in 34-day-old intact male rats, suggesting that in this age group the liver is intrinsically responsive to transcription factors involved in the regulation of GH-dependent, sex-specific CYP gene expression. A higher dose (3.6 µg/g) of GH administered during the prepubertal period was required to elicit a modest effect on somatic growth and gonadal development.Key words: cytochrome P450, CYP2C11, CYP2C12, growth hormone, preputial separation, pubertal development, testosterone.
The role of K+ATP channels in the control of pre- and post-ischemic left ventricular developed pressure in septic rat hearts
Authors: Ismail Jitka A , McDonough Kathleen H
Published: April 2011

Myocardial function is impaired 24 h after the induction of sepsis, however, recovery of left ventricular (LV) function after 35 min of global ischemia is complete. The mechanisms by which this protection occurs are unknown. Ischemic preconditioning, another form of myocardial protection from ischemia/reperfusion (I/R) injury, has been shown to be modulated by ATP-sensitive potassium (K+ATP) channels. To investigate the role of K+ATP channels in the regulation of coronary flow (CF) and protection from I/R injury in septic rat hearts, we assessed the effects of the K+ATP channel antagonist glibenclamide (GLIB) and the agonist cromakalim (CROM) on pre- and post-ischemic CF and left ventricular developed pressure (LVDP). Although GLIB decreased pre-ischemic CF in both control and septic rat hearts, LVDP was unaffected. After I/R, CF was decreased in GLIB-treated control and septic rat hearts and LVDP was more severely depressed in control rat hearts than in septic rat hearts. CROM increased pre-ischemic CF in the septic group although LVDP was unaltered in both groups. After I/R, control rat heart CF was depressed but LVDP completely recovered. Post-ischemic CF in septic rat hearts was elevated compared with vehicle-treated septic rat hearts, but the recovery of LVDP was not improved. These results suggest that K+ATP channels modulate CF in septic rat hearts, but do not mediate cardioprotection as observed in control rat hearts.Key words: K+ATP channel, preconditioning, ischemia, reperfusion, sepsis.
Adult neurogenesis in natural populations
Authors: Boonstra R , Galea L , Matthews S , Wojtowicz J M
Published: April 2011

The dogma that the adult brain produces no new neurons has been overturned, but the critics are still asking, so what? Is adult neurogenesis a biologically relevant phenomenon, or is it perhaps harmful because it disrupts the existing neuronal circuitry? Considering that the phenomenon is evolutionarily conserved in all mammalian species examined to date and that its relevance has been well documented in non-mammalian species, it seems self-evident that neurogenesis in adult mammals must have a role. In birds, it has been established that neurogenesis varies dramatically with seasonal changes in song production. In chickadees, the learning behaviour related to finding stored food is also correlated with seasonal adult neurogenesis. Such studies are still nonexistent in mammals, but the related evidence suggests that neurogenesis does vary seasonally in hamsters and shows sexual differences in meadow voles. To promote studies on natural populations asking fundamental questions of the purpose and function of neurogenesis, we organized a Workshop on "Hippocampal Neurogenesis in Natural Populations" in Toronto in May 2000. The Workshop highlighted recent discoveries in neurogenesis from the lab, and focused on its functional consequences. The consensus at the Workshop was that demonstration of a role for neurogenesis in natural behaviours will ultimately be essential if we are to understand the purpose and function of neurogenesis in humans.Key words: neurogenesis, hippocampus, dentate gyrus, learning, memory, wild population.
Skeletal sensitivity to dietary calcium deficiency is increased in the female compared with the male rat
Authors: Geng W , Wright G L
Published: April 2011

We investigated potential sex differences in bone resorption and the conservation of whole body bone mass in 24-week-old Sprague-Dawley rats maintained on a 1.0% calcium diet and then fed diets containing 0.02, 0.5, 1.0, or 1.75% calcium for 31 days. Lowering dietary calcium from 1.00% to 0.02% doubled whole skeleton bone resorption (urinary 3H-tetracycline loss). Female rats were more sensitive to calcium stress, exhibiting the maximal resorptive response when fed the 0.5% calcium diet, whereas the 0.02% calcium diet was required to elicit this response in males. Despite the evidence of increased bone resorption, whole skeleton mass was unchanged in females and was significantly increased in males, indicating that switching to even the 0.02% calcium diet did not result in an overt loss of total body bone mass. Compared with controls, the skeleton mass of females (97 ± 1.4%) maintained on the 0.02% calcium diet was significantly lower than males (107 ± 2.4%), again suggesting a greater impact of calcium deficiency in females. The calculation of the average percentage growth of selected individual bones in male rats indicated a proportional increase in bone mass between the axial and appendicular skeleton of approximately +4% and +18% in animals maintained on 0.02 and 1.75% diets, respectively. By comparison, female rats consuming the 0.02% calcium diet showed an average 14% loss in axial bone and 7.5% gain in appendicular bone mass. The results indicate increased sensitivity to dietary calcium deficiency in female rats which involves a significant loss in axial bone mass not observed in male rats maintained under similar dietary conditions.Key words: skeleton bone mass, calcium diet, 3H-tetracycline, axial, appendicular, gender, sex.
Chronotropic response to (±)-CGP12177 in right atria of stressed rats
Authors: Santos I N , Spadari-Bratfisch R C
Published: April 2011

Foot-shock stress changes the sensitivity of the rat right atria to β1- and β2-adrenoceptor (AR) agonists. We investigated whether the same stress protocol also changes the atrial sensitivity to the non conventional agonist, (±)-CGP12177. Concentration-response curves to (±)-CGP12177, a β1- and β2-adrenoceptor antagonist with agonist properties at the putative β4-adrenoceptors, were obtained in the absence and presence of propranolol (200 nM or 2 µM), CGP20712A 10 nM plus ICI118,551 50 nM, or CGP20712A (1 µM or 3 µM), in right atria from rats submitted to three daily foot-shock sessions (120 mA pulses of 1.0 s duration applied at random intervals of 5-25 s over 30 min) and killed after the third session. The pD2 for (±)-CGP12177 was not influenced by foot-shock stress. The stimulant effect of (±)-CGP12177 was resistant to blockade by 200 nM and 2 µM (±)-propranolol, and to combined blockade by CGP20712A and ICI118,551. However, in right atria from stressed rats given 200 nM propranolol, the concentration-response curve to the agonist was shifted 2.0-fold to the right. CGP20712A shifted the concentration-response curve to (±)-CGP12177 to the right by 4.6- (1 µM) and 19-fold (3 µM) in atria of control rats, and by 2.2- (1 µM) and 43-fold (3 µM) in atria of stressed rats. Maximum response to CGP12177 was not affected by propranolol or CGP20712A in concentrations ranging from 0.1 nM to 10 µM. These results show that the chronotropic effect of (±)-CGP12177 is mediated by atypical β4-adrenoceptors. In constrast with to β1-and (or) β2-AR, this receptor is resistant to the effects of foot-shock stress, suggesting that the putative β4-AR is a different receptor from a low affinity state of β1-adrenoceptor, as previously proposed, unless both proposed isoforms of β1-adrenoceptor show independent stress-induced behavior.Key words: putative β4-adrenoceptor, low affinity β1-adrenoceptor isoform, stress, right atria, chronotropic response.
Estrogen effect on post-exercise skeletal muscle neutrophil infiltration and calpain activity
Authors: Tiidus Peter M , Holden Dean , Bombardier Eric , Zajchowski Sheri , Enns Deborah , Belcastro Angelo
Published: April 2011

We hypothesized that estrogen administration would attenuate skeletal muscle neutrophil infiltration, indices of muscle membrane disruption, and muscle calpain activity shortly after the termination of exercise. Ovariectomized female rats were implanted with either an estogen pellet (25 mg β-estradiol) or a placebo pellet. Two weeks post-implant, animals were killed either at rest or 1 h after running exercise (60 min at 21 m·min1, 12% grade). The 4 experimental groups (n = 12) used were: unexercised placebo (UP), unexercised estrogen (UE), exercised placebo (EP), and exercised estrogen (EE). Blood samples were analyzed for creatine kinase (CK) activity and estradiol content. Plantaris and gastrocnemius muscles were removed and histochemical determination of neutrophil content or biochemical determination of myeloperoxidase (MPO), glucose-6-phosphate dehydrogenase (G6PD), and calpain-like activity determined. Estrogen supplemented animals had 1020-fold higher circulating estradiol levels than placebo animals. EP animals had significantly higher (P < 0.05) circulating CK activities than EE or unexercised animals. Muscle neutrophil concentrations were significantly (P < 0.01) elevated in EP and EE groups compared with unexercised controls, with EP muscle neutrophil levels also being over 60% greater (P < 0.05) than in EE animals. EP animals also had higher (P < 0.05) muscle MPO activities than unexercised or EE animals. Muscle G6PD activities were not significantly different between any groups. Muscle caplain-like activities were 80% higher (P < 0.01) in EP animals than EE animals with calpain-like activities in EE animals similar to unexercised groups. These results indicate that estrogen supplementation in ovariectomized rats attenuated 1-h post-exercise serum CK activities, muscle neutrophil infiltration, MPO activities, and calpain-like activities when compared with exercised, unsupplemented animals. This supports the possibility of a relationship between estrogen, calpain dependent production of neutrophil chemo-attractant peptides, and 1-h post-exercise skeletal muscle neutrophil infiltration.Key words: neutrophils, calpain, estrogen, skeletal muscle, muscle damage.
Endothelium-dependent desensitization to angiotensin II in rabbit aorta: the mechanisms involved
Authors: Jerez S , Bruno M Peral de , Coviello A
Published: April 2011

The aim of this study was to characterize the role of the endothelium in angiotensin II-desensitization and its mechanisms of action. Rabbit aortic rings were exposed to increasing doses of angiotensin II (Ang II, 109 to 2.5 × 106) to generate two cumulative dose-response curves (CDRC I and II). A 50-min interval separated CDRC I and II. Desensitization was observed at all doses in unrubbed aortic tissue and at lower doses in rubbed aortic tissue. Tachyphylaxis was greater in arteries with endothelium. Treatment of intact rings with L-NG-nitroarginine methyl ester (L-NAME, 104 M) did not prevent this phenomenon. However, indomethacin (105 M) and miconazol (106 M) attenuated Ang II-desensitization. Treatment of unrubbed rings with nifedipine (106 M) and cromakalim (106 M) inhibited the effect of indomethacin. To confirm the involvement of K+ channels, unrubbed and rubbed aortic rings were treated with the KCa2+ blockers apamin (107 M), tetraethylammonium (TEA, 103 M), and iberiotoxin (108 M), and the KATP blocker glibenclamide (105 M). In both arteries apamin, TEA, and glibenclamide abolished the tachyphylaxis without changes in the maximal response. Iberiotoxin diminished Ang II-desensitization in rubbed but not unrubbed arteries. Results from this study suggest that Ang II-desensitization involves endothelium-dependent and -independent mechanisms. Endothelium-dependent desensitization could be mediated by a cyclooxygenase-cytochrome P450 product, which could act by increasing KCa2+ channel activity.Key words: angiotensin II, rabbit aorta, desensitization, endothelium, cyclooxygenase products.
A1 receptor activation decreases fatigue in mammalian slow-twitch skeletal muscle in vitro
Authors: Reading S A , Barclay J K
Published: April 2011

To test the hypothesis that adenosine improves skeletal muscle cell function, we exposed curarized mouse soleus and extensor digitorum longus (EDL) to a range of concentrations of adenosine (109 M to 105 M). Muscles contracted in Krebs-Henseleit bicarbonate buffer (27°C, 95% O2 and 5% CO2) for 500 ms at 50 Hz once every 90 s. Soleus fatigued significantly less with adenosine present at concentrations of 108 M and higher than with the Krebs-Henseleit vehicle control. Adenosine significantly improved force generation or delayed fatigue of EDL only with the initial adenosine challenge. To investigate the receptor population involved, we exposed soleus to agonists specific for A1 receptors (N6-cyclopentyladenosine, CPA), or A2 receptors (CGS 21680 hydrochloride, CGS), or A3 receptors (N6-benzyl-5'-N-ethylcarboxamidoadenosine, BNECA). CPA (A1) significantly decreased fatigue compared with the Krebs-Henseleit vehicle control at concentrations of 109 M and higher. Muscles exposed to the A2 and A3 agonists did not differ from a Krebs-Henseleit plus methanol control. Phenylephrine (106 M), an alpha-adrenergic agonist that increases the concentration of inositol triphosphate (IP3), significantly improved developed force in soleus. Neither a permeable cAMP analog, 8-bromo-cAMP (105 M), nor a beta1 agonist, isoproterenol (106 M), had an effect on force generation in the soleus when compared with a saline control. Thus adenosine slowed fatigue in slow-twitch skeletal muscle through A1 receptors.Key words: N6-cyclopentyladenosine, CGS 21680 hydrochloride, N6-benzyl-5'-N-ethylcarboxamidoadenosine, mouse skeletal muscle in vitro.
Neutrophil response to prolonged exercise in immune-competent and RAG2/γc null mice
Authors: Blank Sally E , Tiidus Peter M , Hoffman-Goetz Laurie
Published: April 2011

The two aims of this study were (i) to compare the effects of prolonged exercise on circulating neutrophil number and muscle myeloperoxidase (MPO) activity between RAG2/γc null and immune-competent mice, and (ii) to evaluate the general suitability of the lymphocyte-deficient RAG2/γc null strain for use in exercise models of immune regulation. RAG2/γc null (male and female) and C57BL/6 (congenic immune-competent, male) mice were assigned to either control (C) or treadmill exercise (EX, 22 m/min, 90 min, 6% grade) groups. EX mice were killed immediately (EX0) or 24 h (EX24) after exercise. RAG2/γc null males had significantly (P < 0.05) fewer circulating CD45+cells and higher %CD45+neutrophils than did C57BL/6 males, independent of exercise. A significant interaction was observed for the effects of exercise and gender on %CD45+neutrophils in the blood. At EX24, gastrocnemius (Gastroc) MPO significantly increased in EX mice. Gastroc MPO activity was 44% and 35% higher in RAG2/γc null vs. C57BL/6 males, and in female vs. male RAG2/γc null mice, respectively. Heart MPO activity did not differ between strains or among treatments. We concluded that the Rag2/γc null strain is a suitable model for future investigations on immune regulation following acute exercise stress.Key words: treadmill exercise, neutrophils, immune-deficient, RAG2/γc null mice.
Oxidations of 17β-estradiol and estrone and their interconversions catalyzed by liver, mammary gland and mammary tumor after acute and chronic treatment of rats with indole-3-carbinol or β-naphthoflavone
Authors: Ritter Clare L , Prigge William F , Reichert Mark A , Malejka-Giganti Danuta
Published: April 2011

Altered cytochrome P450-catalyzed metabolism of 17β-estradiol (E2) and estrone (E1) in the liver and (or) extrahepatic tissues may affect estrogen-sensitive tumorigenesis. We examined the effects of oral treatments of (i) indole-3-carbinol (I3C) at 250 or 500 mg/kg or β-naphthoflavone (β-NF) at 40 mg/kg of body weight (bw)/day from 51 to 54 days of age (acute regimen), and (ii) I3C at 250 mg/kg or β-NF at 20 mg/kg bw given 3x/week from 10 to 22 weeks of age (chronic regimen) in female Sprague-Dawley rats. We determined the effects of these treatments on the P450 content and P450 (CYP)-specific activities in the liver, P450-dependent metabolism of E2 and E1 by the liver and mammary gland, and interconversion of E1 and E2 catalyzed by 17β-hydroxysteroid dehydrogenase (17β-HSD) in these tissues and malignant mammary tumors. I3C at the two levels of acute regimen elicited similar responses. Acute and chronic treatments with I3C, but not β-NF, increased P450 content ~2-fold. I3C, and to a lesser extent β-NF, increased CYP1A1 and CYP1A2 probe activities in liver up to 117- and 27- fold, respectively, and after acute regimens, that of CYP3A by ~1.8-fold. I3C also increased activity of CYP2B up to 100-fold. Overall hepatic metabolism of E2 and E1, which was ~2-fold greater at 55 than 155 days of age, was increased (~2.8-fold) by I3C with 2-, 4-, 16α-, 6α-, 6β-, and 15α-hydroxy (OH) comprising [Formula: see text]54, 3, 2, ~2, ~5, 7, and 2%, respectively, of E1 and E2 metabolites. Acute regimens of β-NF increased 2- and 15α-OH-E2 (62 and 5% of total) from E2 and 2-, 4-, and 6α-OH-E1 + 6β-OH-E1 (32, 13, and 4% of total) from E1. Mammary gland metabolized E2 to E1 and small amounts of 15α-, 4-, 16α-, 6β-, and 6α-OH-E2. After the acute IC3 regimen, E2 was also converted to 2-OH-E2. 17β-HSD-catalyzed oxidation of E2 was favored in the liver and reduction of E1 was favored in mammary gland and tumor (= 1% of hepatic activity). An increased (~2-fold) ratio of reductive to oxidative activities in malignant mammary tumors by chronic I3C regimen may stimulate tumor growth. This is the first report showing that after chronic oral regimens, the I3C-, but not β-NF-, induced changes in CYP complement led to elevated E2 and E1 metabolism. The persistent effects of increased putative carcinogenic and estrogenic 4- and 16α-OH as well as 6α- and 6β-OH-E2 and 6β-OH-E1 might counteract those of the less estrogenic 2-OH metabolites, thus accounting for the lack of suppression of mammary tumorigenesis by I3C in our previous study.Key words: estrogen metabolism, P450, 17β-hydroxysteroid dehydrogenase, indole-3-carbinol, β-naphthoflavone.
Contractile function in vitro of slow-twitch skeletal muscle from weanling mice subjected to wasting malnutrition
Authors: Fischer J W , Reading S A , Hillyer L , Woodward B , Barclay J K
Published: April 2011

Our hypothesis was that malnutrition sufficient to produce weight loss in weanling mice would decrease the ability of slow-twitch skeletal muscle to develop and maintain force. We isolated muscles from 3 groups (n = 5) of weanling C57BL/6J mice of both sexes (i) mice at 19 days of age serving as zero-time or baseline controls (CONT) (ii) mice fed for the next 14 days with a low-protein diet that produces features of incipient kwashiorkor (LPD) and (iii) mice fed for the next 14 days with a complete diet (NORM). Muscles were also obtained from 5 adult mice 79 months of age (MAT). We stimulated the soleus at 50 Hz for 500 ms at 0.6 tetanic contractions per min (tet·min1), 6 tet·min1, and 30 tet·min1in Krebs-Henseleit bicarbonate buffer at 27°C gassed with 95% O2and 5% CO2. The initial developed force (mN·mm2) at 0.6 tet·min1did not differ across groups (CONT 211.7 ± 16.0, LPD 274.2 ± 41.6, NORM 246.8 ± 38.0, MAT 210.8 ± 10.6). The fatigue rate (mN·mm2·min1) at 6 tet·min1was significantly slower in muscles from CONT (0.6 ± 0.3) and LPD (0.6 ± 0.4) than in NORM (2.4 ± 0.6) and MAT (2.3 ± 0.2). At 30 tet·min1, the fatigue rate (mN·mm2·min1) did not differ across groups (CONT 2.4 ± 0.5, LPD 2.7 ± 0.5, NORM 2.5 ± 0.4, MAT 2.0 ± 0.2). After stimulation at 6 tet· min1and 30 tet·min1, only muscles from CONT and LPD recovered to 100%. Because muscles from LPD mice developed equal force, fatigued less, and recovered from fatigue to a greater extent than muscles from NORM mice, we rejected the hypothesis. The function of the tissue remaining in the muscles from LPD mice approximated that of muscles from mice at 19 days of age rather than muscles from either mice of the same age fed a complete diet or adult mice.Key words: developed force, fatigue, recovery from fatigue.
A comparison of no-flow and low-flow ischemia in the rat heart: an energetic study
Authors: Consolini A E , Marquez M T , Ponce-Hornos J E
Published: April 2011

Heat production under no-flow ischemia (ISCH) and under hypoperfusion (HYP) conditions was measured in single isovolumetric contractions of perfused rat ventricles at 25°C. Resting heat production (Hr) and resting pressure decreased when the perfusion rate was reduced from 6 to 1.5 mL·min-1 or lower flows (HYP) and by ISCH. Maximal developed pressure (P) decreased to 29% and 20% of control by HYP at 0.8 mL·min1 and ISCH, respectively. The tension-independent heat (TIH) fraction attributed to Ca2+-binding, measured during single contractions, decreased under HYP with an increase in the ratio between the maximum relaxation rate and P (P/P ratio). The TIH fractions (attributed to Ca2+ binding and Ca2+ removal processes) decreased under ISCH. The long duration TIH fraction associated with Ca2+-dependent mitochondrial activity disappeared at flow rates of 1.5 mL·min1 or lower. The ratio between the tension-dependent energy release and P was decreased by ISCH but not by HYP, indicating that under ISCH there was an improvement in contractile economy, but this was not modified by HYP. Overall, the results indicate that no-flow and low-flow ischemias are energetically different models. While the contractile failure under HYP seems to be related to a decrease in myofilament Ca2+ sensitivity, under ISCH it appears to be related to decreased cytosolic Ca2+ availability combined with a more noticeable effect on a fraction of energy that has been attributed to mitochondrial activity. Furthermore, mechanical and energetic responses of both models (i.e., ISCH and HYP) found in the present work were not the same as those previously observed in severe hypoxia so that all these models should not be used indistinctly.Key words: calorimetry, hypoperfusion, ischemia, muscle economy, tension-dependent heat, tension-independent heat.
Effect of progesterone on the contractile response of isolated pulmonary artery in rabbits
Authors: Li Hong-Fang , Zheng Tian-Zhen , Li Wei , Qu Song-Yi , Zhang Chen-Lie
Published: April 2011

The purpose of this study was to assess the direct effect of progesterone on rabbit pulmonary arteries and to examine the mechanism of its action. Rings of pulmonary artery from male rabbits were suspended in organ baths containing Krebs solution, and isometric tension was measured. The response to progesterone was investigated in arterial rings contracted with noradrenaline (NA), KCl, and CaCl2. The effects of endothelium, nitric oxide(NO), prostaglandins, cyclic GMP(cGMP), and the adrenergic β-receptor on progesterone-induced relaxation were also assessed. Progesterone inhibited the vasocontractivity to NA, KCl, and CaCl2, and relaxed rabbit pulmonary artery. The relaxing response of progesterone in pulmonary artery was significantly reduced by removal of endothelium, inhibitors of nitric oxide synthase and guanylate cyclase, but not by prostaglandin synthase inhibitor and blockage of the adrenergic β-receptor. In Ca2+-free (0.1 mM EGTA) Krebs solution, progesterone inhibited NA-induced contraction that was intracellular Ca2+-dependent, but didn't affect the contraction of extracellular Ca2+-dependent component. Our results suggest that progesterone induces relaxation of isolated rabbit pulmonary arteries partially via NO and cGMP. Progesterone may also inhibit Ca2+influx through potential-dependent calcium channels (PDCs) and Ca2+release from intracellular stores.Key words: progesterone, pulmonary artery, Ca2+channel, endothelium.
Caffeine ingestion elevates plasma insulin response in humans during an oral glucose tolerance test
Authors: Graham Terry E , Sathasivam Premila , Rowland Mary , Marko Natasha , Greer Felicia , Battram Danielle
Published: April 2011

We tested the hypothesis that caffeine ingestion results in an exaggerated response in blood glucose and (or) insulin during an oral glucose tolerance test (OGTT). Young, fit adult males (n = 18) underwent 2 OGTT. The subjects ingested caffeine (5 mg/kg) or placebo (double blind) and 1 h later ingested 75 g of dextrose. There were no differences between the fasted levels of serum insulin, C peptide, blood glucose, or lactate and there were no differences within or between trials in these measures prior to the OGTT. Following the OGTT, all of these parameters increased (P [Formula: see text] 0.05) for the duration of the OGTT. Caffeine ingestion resulted in an increase (P [Formula: see text] 0.05) in serum fatty acids, glycerol, and plasma epinephrine prior to the OGTT. During the OGTT, these parameters decreased to match those of the placebo trial. In the caffeine trial the serum insulin and C peptide concentrations were significantly greater (P [Formula: see text] 0.001) than for placebo for the last 90 min of the OGTT and the area under the curve (AUC) for both measures were 60 and 37% greater (P [Formula: see text] 0.001), respectively. This prolonged, increased elevation in insulin did not result in a lower blood glucose level; in fact, the AUC for blood glucose was 24% greater (P = 0.20) in the caffeine treatment group. The data support our hypothesis that caffeine ingestion results in a greater increase in insulin concentration during an OGTT. This, together with a trend towards a greater rather than a more modest response in blood glucose, suggests that caffeine ingestion may have resulted in insulin resistance.Key words: adenosine, skeletal muscle, methylxanthines, glucose uptake, diabetes.
Mechanical load-induced alterations in B-type natriuretic peptide gene expression
Authors: Tokola Heikki , Hautala Nina , Marttila Minna , Magga Jarkko , Pikkarainen Sampsa , Kerkelä Risto , Vuolteenaho Olli , Ruskoaho Heikki
Published: April 2011

Atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide are the known members of the mammalian natriuretic peptide system. Like ANP, BNP is a natriuretic and diuretic hormone that also causes peripheral vasodilation and inhibition of the sympathetic and renin-angiotensin systems. Although originally isolated from porcine brain, the BNP gene is expressed in a specific manner in cardiac myocytes in both the atria and the ventricles, but it is mainly released from the ventricles. The major determinant of BNP secretion is wall stretch, and the levels of BNP mRNA increase substantially in response to cardiac overload. In the clinical setting, BNP appears to be the most powerful neurohumoral predictor of left-ventricular function and prognosis. An acute increase in BNP gene expression occurs within 1 h and mimics the rapid induction of proto-oncogenes in response to hemodynamic stress. BNP can be used as a myocyte-specific marker to identify mechanisms that couple acute mechanical overload to alterations in cardiac gene expression. This paper is focused on the mechanisms that regulate BNP gene expression in cardiac overload. Particularly, autocrine-paracrine factors as well as cytoplasmic signaling pathways and transcription factors involved in mechanical stretch-induced BNP gene expression are discussed.Key words: gene expression, mechanical load, natriuretic peptides, paracrine factors, transcription factors.
Dynamics of internalization and sequestration of guanylyl cyclase/atrial natriuretic peptide receptor-A
Authors: Pandey Kailash N
Published: April 2011

The guanylyl cyclase/natriuretic peptide receptor-A (NPRA), also referred to as GC-A, is a single polypeptide molecule. In its mature form, NPRA resides in the plasma membrane and consists of an extracellular ligand-binding domain, a single transmembrane-spanning region, and intracellular cytoplasmic domain that contains a protein kinase-like homology domain (KHD) and a guanylyl cyclase (GC) catalytic active site. The binding of atrial natriuretic peptide (ANP) to NPRA occurs at the plasma membrane; the receptor is synthesized on the polyribosomes of the endoplasmic reticulum, and is presumably degraded within the lysosomes. It is apparent that NPRA is a dynamic cellular macromolecule that traverses through different compartments of the cell through its lifetime. This review describes the experiments addressing the interaction of ANP with the NPRA, the receptor-mediated internalization and stoichiometric distribution of ANP-NPRA complexes from cell surface to cell interior, and its release into culture media. It is hypothesized that after internalization, the ligand-receptor complexes dissociate inside the cell and a population of NPRA recycles back to plasma membrane. Subsequently, some of the dissociated ligand molecules escape the lysosomal degradative pathway and are released intact into culture media, which reenter the cell by retroendocytotic mechanisms. By utilizing the pharmacologic and physiologic perturbants, the emphasis has been placed on the cellular regulation and processing of ligand-receptor complexes in intact cells. I conclude the discussion by examining the data available on the utilization of deletion mutations of NPRA cDNA, which has afforded experimental insights into the mechanisms the cell utilizes in modulating the expression and functioning of NPRA.Key words: atrial natriuretic peptide receptor-A, guanylyl cyclase receptors, ANP-binding, internalization and recycling of receptor, lysosomal hydrolysis.
Signaling mechanisms underlying strain-dependent brain natriuretic peptide gene transcription
Authors: Liang Faquan , Kovacic-Milivojevic Branka , Chen Songcang , Cui Junfeng , Roediger Fred , Intengan Hope , Gardner David G
Published: April 2011

Activation of brain natriuretic peptide (BNP) gene promoter activity represents one of the earliest and most reliable markers of ventricular cardiac myocyte hypertrophy. We recently demonstrated that mechanical strain increases immunoreactive BNP secretion, steady-state BNP mRNA levels and BNP gene transcriptional activity in neonatal rat myocyte cultures. We have also shown that strain-dependent BNP gene transcription is critically dependent on the functional integrity of a number of integrins (specfically β1, β3, and αvβ5 integrins) present on the surface of cardiac myocytes. When used alone, each of these antibodies resulted in a significant reduction in strain-dependent activation of a transfected hBNP-luciferase reporter and inhibition of a number of signaling pathways that have been linked to stimulation of this reporter (e.g., extracellular signal regulated kinase and c-Jun amino terminal kinase). The present study shows that combinations of these antibodies resulted in further reductions in hBNP gene promoter activity and inhibition of the relevant signaling cascades. These studies provide further support for the importance of integrin-matrix interactions in promoting strain-dependent changes in cardiac myocyte gene transcription.Key words: mechanical strain, brain natriuretic peptide, integrins, mitogen-activated protein kinase, cardiac myocyte.
Magnesium sulfate attenuates increased blood-brain barrier permeability during insulin-induced hypoglycemia in rats
Authors: Kaya Mehmet , Küçük Mutlu , Kalayci Rivaze Bulut , Cimen Vedat , Gürses Candan , Elmas Imdat , Arican Nadir
Published: April 2011

Magnesium probably protects brain tissue against the effects of cerebral ischemia, brain injury and stroke through its actions as a calcium antagonist and inhibitor of excitatory amino acids. The effects of magnesium sulfate on cerebrovascular permeability to a dye, Evans blue, were studied during insulin-induced hypoglycemia with hypothermia in rats. Hypoglycemia was induced by an intramuscular injection of insulin. After giving insulin, each animal received MgSO4 (270 mg/kg) ip, followed by a 27 mg/kg dose every 20 min for 2.5 h. Plasma glucose and Mg2+ levels of animals were measured. Magnesium concentrations increased in the serum following MgSO4 administration (6.05 ± 0.57 vs. 2.58 ± 0.14 mg/dL in the Mg2+ group, and 7.14 ± 0.42 vs. 2.78 ± 0.06 mg/dL in the insulin + Mg2+ group, P < 0.01). Plasma glucose levels decreased following hypoglycemia (4 ± 0.66 vs. 118 ± 2.23 mg/dL in the insulin group, and 7 ± 1.59 vs. 118 ± 4.84 mg/dL in the insulin + Mg2+ group, P < 0.01). Blood-brain barrier permeability to Evans blue considerably increased in hypoglycemic rats (P < 0.01). In contrast, blood-brain barrier permeability to Evans blue was significantly reduced in treatment of hypoglycemic rats with MgSO4 (P < 0.01). These results indicate that Mg2+ greatly reduced the passage of exogenous vascular tracer bound to albumin into the brain during hypoglycemia with hypothermia. Mg2+ could have protective effects on blood-brain barrier permeability against insulin-induced hypoglycemia.Key words: blood-brain barrier, hypoglycemia, Mg2+, Evans-blue.
Effects of 4-hydroxyandrostenedione and hyperstimulation with pregnant mare serum gonadotrophin on early embryonic development in rats
Authors: Tong Terry Y.Y , Goh Victor H.H
Published: April 2011

A possible role of high oestradiol levels in mediating the adverse effects of hyperstimulation with pregnant mare serum gonadotrophin (PMSG) on early embryonic development in the rat was investigated using an aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA), to inhibit endogenous oestradiol production. Three experiments were conducted in this study. In the first, varying doses of 4-OHA were administered either concurrently with human chorionic gonadotropin (hCG) to pro-oestrus female rats hyperstimulated at early di-oestrus stage with 20 IU PMSG or alone into nonhyperstimulated pro-oestrus females. At high doses of 1000, 2000, or 5000 µg/rat, 4-OHA substantially improved the survival of embryos in hyperstimulated females, while low doses of 100 and 500 µg/rat were ineffective. The protective effect of 4-OHA on embryo count was optimum at 2000 µg. When administered alone, only the highest dose of 5000 µg/rat 4-OHA increased embryo count. In the second experiment, higher doses of PMSG were studied (30 or 40 IU), with or without 5000 µg/rat 4-OHA given at the time of hCG injection. PMSG proved to be more detrimental with increasing dose, and 5000 µg/rat 4-OHA was able to rescue embryos from death in the 30, but not 40, PMSG group. In the third experiment, the influence of the timing of 4-OHA treatment on its ability to improve the embryo count in hyperstimulated females was examined by introducing 4-OHA 24 h earlier, rather than at the time of hCG treatment. The results showed the importance of timing of 4-OHA administration, as 5000 µg/rat 4-OHA was able to restore embryo survival in the 40 PMSG hyperstimulated group only when it was administered 24 h before hCG injection. Together, these results highlighted that 4-OHA, when administered at the appropriate time and dose, could reverse the negative effects of hyperstimulation from PMSG on early embryonic development. This may be due to its potent aromatase inhibiting properties that lead to the suppression of oestrogen production, thereby alleviating the supraphysiological level of oestradiol, which is typically present in PMSG-treated females. Interestingly, 4-OHA treatment on its own was able to positively influence embryo count when given at a high dose of 5000 µg/rat, and this may be associated with its weak androgenic properties. In conclusion, this study supports the hypothesis that excessive oestradiol is responsible for the negative effects of hyperstimulation with PMSG on early embryonic development.Key words: 4-hydroxyandrostenedione, embryonic development, PMSG, rat.
Regulation of leukocyte adhesion to heart by the tripeptides feG and feG(NH2)
Authors: Mathison Ronald , Woodman Richard , Davison Joseph S
Published: April 2011

The role of the D-isomeric form of the salivary gland tripeptide FEG (feG) and its carboxyl-amidated derivative, feG(NH2), in regulating leukocyte adherence to nonfixed atrial slices from Sprague-Dawley rats was examined under static conditions. Optimal binding of the leukocytes was seen if the leukocytes were treated with platelet activating factor (PAF; 10-9M). The increased adherence of PAF-treated peripheral blood leukocytes was totally inhibited by both feG and feG(NH2) (10-9M), as well as by antibodies against CD18 and CD49d. In contrast, the binding of peritoneal leukocytes was blocked only by CD49d antibody. Circulating leukocytes obtained from lipopolysaccharide (LPS) treated (2 mg/kg ip) rats did not bind to atrial slices obtained from normal hearts, but readily bound to atrial slices obtained from LPS-treated rats. This leukocyte binding was inhibited by in vivo feG treatment (100 µg/kg ip, 24 h before harvest) or by treating the isolated cells with feG (10-9M). The amidated peptide feG(NH2) reduced neutrophil accumulation in the atrium elicited by ip injection of LPS, whereas feG was ineffective. The reduction in neutrophil infiltration into the myocardium by feG(NH2) and the prevention of leukocyte interaction with myocytes seen with both feG and feG(NH2) probably results in hindered leukocyte migration in the inflamed heart, resulting in less tissue damage. The inhibition by these tripeptides on neutrophil adhesion to myocytes suggests that salivary glands hormones regulate the severity of cardiac inflammation.Key words: endotoxemia, inflammation, salivary glands, leukocytes, heart, adhesion.
Oxygen sensitive chemoreceptors in the first gill arch of the tadpole,Rana catesbeiana
Authors: Straus Christian , Wilson Richard JA , Remmers John E
Published: April 2011

Spike frequency was recorded in the nerve of the isolated superfused first gill arch of the bullfrog larva, Rana catesbeiana and the response to different superfusate [Formula: see text] was evaluated. In the metamorphic tadpole, spike frequency increased significantly when the superfusate [Formula: see text] was decreased (mean ± SEM): 8.5 ± 1.6 Hz at 650 Torr, 11.7 ± 1.9 Hz at 140 Torr, 13.3 ± 1.8 Hz at 65 Torr, 14.8 ± 2.4 Hz at 0 Torr (ANOVA, p = 0.0002). The O2sensitive chemoreceptor stimulants NaCN and almitrine also increased the spike frequency. This study demonstrates the presence of O2sensitive chemoreceptors in the first gill arch of the tadpole.Key words: tadpole, Rana catesbeiana, gill, chemoreceptor, oxygen.