bluuebunny/crossref_metadata_2025 huggingface dataset:
Amantadine acetylation may be effected by acetyltransferases other than NAT1 or NAT2
Authors: Bras Alvaro PM , Hoff Harry R , Aoki Fred Y , Sitar Daniel S
Published: April 2011

Amantadine is a drug with a primary amino group, and consequently a likely candidate for metabolism by acetylation. This study assessed the possibility that a person's polymorphic (NAT2) acetylator phenotype could be used to predict the extent of amantadine acetylation. Thirty-eight normal, healthy volunteers were NAT2 acetylator phenotyped with sulfapyridine. Of the six fastest (75-86%) and six slowest (34-40%) sulfapyridine acetylators, two and three, respectively, had acetylamantadine present (18-338 µg) in the 8-h urine collection. There was no correlation between NAT2 acetylator phenotype and amantadine acetylation (p < 0.5), and no difference in the total urine amantadine excreted over 8 h between acetylators and nonacetylators (28.3 ± 9.7 vs. 30.4 ± 9.6 mg, respectively, mean ± SD). Acetylamantadine represented 0.1-1.5% (median 0.5%) of urinary drug content over 8 h. Our data confirm that amantadine is acetylated in humans and demonstrate for the first time that the extent is not correlated with NAT2 acetylator phenotype. Parallel in vitro enzyme studies indicate the possibility that neither NAT1 nor NAT2 is responsible for acetylation of amantadine.Key words: amantadine, acetylation, conjugation, drug metabolism.
Higher mitochondrial fatty acid oxidation following intermittent versus continuous endurance exercise training
Authors: Chilibeck P D , Bell G J , Farrar R P , Martin T P
Published: April 2011

It has been well documented that skeletal muscle fatty acid oxidation can be elevated by continuous endurance exercise training. However, it remains questionable whether similar adaptations can be induced with intermittent interval exercise training. This study was undertaken to directly compare the rates of fatty acid oxidation in isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria following these different exercise training regimes. Mitochondria were isolated from the gastrocnemius-plantaris muscles of male Sprague-Dawley rats following exercise training 6 days per week for 12 weeks. Exercise training consisted of either continuous, submaximal, endurance treadmill running (n = 10) or intermittent, high intensity, interval running (n = 10). Both modes of training enhanced the oxidation of palmityl-carnitine-malate in both mitochondrial populations (p < 0.05). However, the increase associated with the intermittent, high intensity exercise training was significantly greater than that achieved with the continuous exercise training (p < 0.05). Also, the increases associated with the IMF mitochondria were greater than the SS mitochondria (p < 0.05). These data suggest that high intensity, intermittent interval exercise training is more effective for stimulation of fatty acid oxidation than continuous submaximal exercise training and that this adaptation occurs preferentially within IMF mitochondria.Key words: muscle, subsarcolemmal mitochondria, intermyofibrillar mitochondria.
Acid-base regulation and control of ventilation in human pregnancy
Authors: Wolfe Larry A , Kemp Justin G , Heenan Aaron P , Preston Robert J , Ohtake Patricia J
Published: April 2011

The purposes of this review were twofold: to apply modern physicochemical principles to explain changes in acid-base regulation and the control of ventilation in human pregnancy; and to demonstrate the value of pregnancy as a model for the study of endocrine effects on physiological control systems. Application of P.A. Stewart's approach (P.A. Stewart. Can. J. Physiol. Pharmacol. 61: 1444-1461, 1983) shows that lower values of plasma hydrogen ion concentration ([H+]) observed at rest and in association with exercise in pregnancy are the result of lower values for carbon dioxide tension (PCO2) and total weak acid ([Atot]). This effect is partly offset by a lower strong ion difference ([SID]). The ability to predict plasma [H+] at rest and following strenuous exercise in pregnancy (J.G. Kemp, F.A. Greer, and L.A. Wolfe. J. Appl. Physiol. 83: 644-651, 1997) supports the validity of Stewart's approach. Jennings and associates (D.B. Jennings. Can. J. Physiol. Pharmacol. 72: 1499-1512, 1994) have further demonstrated in animal models the involvement of plasma osmolality and circulating levels of angiotensin II (ANG II) and arginine vasopressin (AVP) in the chemical control of ventilation. We hypothesize that pregnancy-induced increases in respiratory sensitivity to carbon dioxide are the combined result of reduced plasma osmolality, reduced cerebrospinal fluid [SID], and augmented circulating levels of progesterone, ANG II, and AVP.Key words: human gestation, hydrogen ion concentration, strong ion difference, osmolality, angiotensin II, arginine vasopressin, progesterone.
PACAP enhances stimulation-induced norepinephrine release in canine pancreas in vivo
Authors: Yamaguchi Nobuharu , Fukushima Yuka
Published: April 2011

The present study was to investigate whether pituitary adenylate cyclase activating polypeptide (PACAP) can modify norepinephrine (NE) release in response to pancreatic nerve stimulation in anesthetized dogs. Plasma catecholamine concentrations in aortic and superior pancreaticoduodenal (SPD) venous blood were determined by a high performance liquid chromatography method. SPD venous blood flow was measured with an electromagnetic flowmeter. Pancreatic nerves were directly stimulated for 1 min (2 ms, 12 V) at various frequencies at the level of the SPD artery. Various doses of PACAP1-27 (PACAP27) were locally infused into the pancreas through the SPD artery. Nerve stimulation significantly increased both SPD venous NE concentration and its output from the pancreas in a frequency-dependent manner. With PACAP27 alone, neither SPD venous NE concentration nor its output changed significantly following the local administration of PACAP27 at any dose tested. In the presence of PACAP27, however, the net increases in NE concentration and its output in response to nerve stimulation at 2 Hz were significantly enhanced in a dose-dependent manner. The enhanced NE responses to nerve stimulation by PACAP27 were thus significantly greater than those obtained from the group receiving either PACAP27 or stimulation alone. Increases in NE concentration and its output induced by local administration of tyramine were virtually abolished by desipramine, a neural amine uptake inhibitor. However, the NE response to tyramine was not diminished by PACAP27. The results indicate that PACAP27 enhances the stimulation-induced NE release in the pancreas, and that this facilitatory effect of PACAP27 does not result from an inhibition of the neural amine uptake mechanism. The study suggests that PACAP receptor-mediated mechanisms may be involved either directly or indirectly in the local modulation of neural NE release in the canine pancreas in vivo.Key words: presynaptic, sympathetic nerve, neuropeptide, tyramine, reuptake, anesthetized dog.
Tumor-enhancing effects of cholic acid are exerted on the early stages of colon carcinogenesis via induction of aberrant crypt foci with an enhanced growth phenotype
Authors: Baijal P K , Clow E P , Fitzpatrick D W , Bird R P
Published: April 2011

The objective of the study was to establish whether cholic acid (CHA) enhanced colonic tumor incidence in the early phase of carcinogenesis. Male, Sprague-Dawley rats (n = 180) were injected twice with azoxymethane (AOM) (15 mg·kg-1 body weight·week-1, s.c., given 1 week apart). Following the first AOM injection, animals were randomly assigned to two groups, control AIN-93G diet (CON) or control diet containing 0.2% CHA by weight (CHA). Three weeks after the first injection, 20 animals (10 animals/group) were killed and aberrant crypt foci (ACF) were enumerated. The remaining animals were further subdivided and animals randomly assigned to CON or CHA diets, creating four treatments: CON-CON, CON-CHA, CHA-CHA, and CHA-CON. After 3, 12, and 20 weeks (following the first carcinogen injection), the animals were killed and the number and crypt multiplicity of ACF enumerated. Macroscopic tumors were evaluated at week 20. Total ACF were not different between groups. Average crypt multiplicity and medium (4-6 crypts/focus) and large (>= 7 crypts/focus) ACF were greater in CHA-CHA and CHA-CON compared with CON-CON and CON-CHA (p < 0.01). Transient exposure to CHA (CHA-CON) was sufficient to induce development of ACF with an accelerated growth phenotype and elicit a tumor-enhancing effect. CHA-CHA had the highest tumor incidence (82.8%, p < 0.05) followed by CHA-CON (56.7%, p < 0.05), and tumor multiplicity and number of tumors per rat in CHA-CON were similar to CHA-CHA (2.29 and 1.3 versus 2.33 and 1.9, respectively). Delayed intervention with CHA (CON-CHA) produced a tumor outcome similar to CON-CON (31 and 30%, respectively), it did not enhance colonic tumor incidence. Taken collectively these results suggest CHA was effective in enhancing colon carcinogenesis during early phases and ineffective in post-initiation phases.Key words: aberrant crypt foci, cholic acid, colon, tumors.
Prostaglandin E2 inhibition of fetal breathing movements is not sustained during prolonged reduced uterine blood flow in sheep
Authors: Watson Carole S , Homan Jacobus H , White Susan E , Challis John R , Bocking Alan D
Published: April 2011

Fetal breathing movements (FBM) are inhibited by both exogenous prostaglandin E2 (PGE2) and ethanol in sheep. Maternal ethanol exposure in late-gestation sheep also increases fetal [PGE2]. However, during prolonged reduced uterine blood flow (RUBF) when [PGE2] in fetal plasma is already elevated, FBM are not inhibited by ethanol. These experiments were designed, therefore, to test the hypothesis that the FBM response to PGE2 is also diminished during RUBF. PGE2 (594 ± 19 ng·min-1·kg-1 fetal body weight) was infused for 6 h into the jugular vein of RUBF (PO2 = 14 ± 1 mmHg (1 mmHg = 133.3 Pa); n = 7) and control (PO2 = 22 ± 1 mmHg (p < 0.01); n = 7) ovine fetuses, and the effect on FBM, electrocortical (ECoG), and electroocular activities was determined. The infusion of PGE2 increased plasma [PGE2] from 881 ± 162 to 1189 ± 114 pg·mL-1 in RUBF fetuses and from 334 ± 72 to 616 ± 118 pg·mL-1 (p < 0.05) in control fetuses. FBM were initially inhibited by PGE2 from 22.5 ± 9.4 and 17.9 ± 6.5% of the time to 6.9 ± 2.4 and 0.5 ± 0.4% (p < 0.01) in RUBF and control fetuses, respectively. FBM remained inhibited in control fetuses throughout the infusion but returned to baseline incidence in RUBF fetuses in the last 2 h of the infusion. These results are consistent with the hypothesis that one component of the adaptative mechanisms of the fetus to prolonged RUBF is an altered response of FBM to exogenous PGE2. We speculate that the lack of a sustained inhibition in FBM during RUBF with infusion of PGE2 may be a result of an alteration in brainstem receptor function or number or local PGE2 removal.Key words: fetal breathing movements, prostaglandin E2, hypoxia, reduced uterine blood flow, ethanol, fetal behaviour.
Effects of norepinephrine on lung liquid production by in vitro lungs from fetal guinea pigs
Authors: Doe S , Woods B , Perks A M
Published: April 2011

Lungs from near-term fetal guinea pigs (61 ± 2 days of gestation) were supported in vitro for 3 h; lung liquid production was monitored by a dye dilution method. Untreated control preparations produced fluid at 1.38 ± 0.30 mL·kg-1 body weight·h-1, with no significant change (ANOVA; regression analysis); those given 1.24 × 10-9 or 1.24 × 10-8 M norepinephrine during the middle hour showed no significant change, but those given concentrations between 5.24 × 10-8 and 1.24 × 10-5 M all showed significant reductions or fluid reabsorption (based on 42 fetuses). The responses showed a linear relationship with the log concentration (r = 0.97). They appeared to involve alpha-adrenoreceptors, since responses to 10-7 M norepinephrine were unaffected by 10-6 M propranolol, but those to 10-7 and 1.24 × 10-6 M norepinephrine were abolished by 10-6 and 1.78 × 10-5 M phentolamine, respectively (based on 48 fetuses). Activation was through alpha2-adrenoreceptors, since responses to 10-7 and 10-5 M norepinephrine were abolished by 10-4 M yohimbine, but not by 10-5 M prazosin (based on 60 fetuses). The results show that norepinephrine is able to reduce lung liquid production when at plasma levels present at birth, and that it can produce reabsorption; unlike epinephrine, there was no reduction in responses at high concentrations. This work reintroduces a neglected factor, norepinephrine, into possible controls of lung liquid reabsorption, and opens up the potential for neural controls.Key words: fetus, norepinephrine, adrenoreceptors, lung liquid.
Nimodipine inhibits the pressor activity of diaspirin-crosslinked hemoglobin (DCLHb) in the rat
Authors: Rioux Francis , St-Pierre Mélanie , Harvey Nathalie , Moisan Steve , Burhop Kenneth E , Drapeau Guy
Published: April 2011

Impaired nitric oxide (NO) activity is associated with an increase in blood pressure in rats. Voltage-regulated calcium channels are believed to participate in this hemodynamic event. To further test this hypothesis, we examined the effect of nimodipine and verapamil (calcium antagonists) on the pressor activity of diaspirin-crosslinked hemoglobin (DCLHb), a well-known NO scavenger, in anesthetized rats. Nimodipine, the most potent of the two calcium antagonists used, was also tested against phenylephrine (alpha1-adrenoceptor agonist). The pressor effect of DCLHb was reduced markedly by nimodipine and verapamil, whereas that elicited by phenylephrine, particularly the tonic phase of its pressor response, was resistant to blockade by nimodipine. The bradycardia and tachycardia associated with the pressor effects of DCLHb and phenylephrine, respectively, were not affected by nimodipine. The pressor effect elicited by DCLHb and its alteration by nimodipine were also examined in rats pretreated with 100% O2. This treatment was found to potentiate the pressor effect of DCLHb. However, this synergism did not impair the inhibitory action of nimodipine towards the pressor activity of DCLHb. Altogether these results suggest that the pressor activity of DCLHb in our animal model might involve the participation of voltage-regulated calcium channels.Key words: hemoglobin, nitric oxide, calcium channels, blood pressure, diaspirin-crosslinked hemoglobin.
Soy protein isolate in the presence of cornstarch reduces body fat gain in rats
Authors: Hurley Christine , Richard Denis , Deshaies Yves , Jacques Hélène
Published: April 2011

The objective of the present study was to determine the combined effects of dietary protein and carbohydrate sources on total body energy and protein and fat gains as well as on plasma insulin and glucose and tissue lipoprotein lipase activity in male Sprague-Dawley rats fed semipurified diets for 28 days. The diets varied in both protein and carbohydrate sources, namely, casein-cornstarch, casein-sucrose, soy protein isolate (SPI) - cornstarch, SPI-sucrose, cod protein - cornstarch, and cod protein - sucrose. When SPI was combined with cornstarch, lower total body energy and fat gains were observed compared with the combination of either casein and sucrose, casein and cornstarch, or SPI and sucrose. Plasma glucose and insulin concentrations in addition to total and metabolizable energy intake and body weight gain were lower in rats fed the SPI-cornstarch diet than in those fed the casein-sucrose diet. Feeding the SPI-cornstarch diet compared with feeding either the casein-cornstarch or the SPI-sucrose diet also caused lower plasma glucose concentrations and a concomitant trend ( p = 0.06) to reduced energy intake and body weight gain. Therefore, the reducing effects of the SPI-cornstarch diet compared with the casein-cornstarch, the casein-sucrose, and the SPI-sucrose diets on body energy and fat gains may result from reductions in energy intake and in plasma glucose concentrations.Key words: dietary proteins, soy protein, dietary carbohydrates, body fat, plasma glucose, plasma insulin.
Evidence of nitric oxide, a flow-dependent factor, being a trigger of liver regeneration in rats
Authors: Wang H Helen , Lautt W Wayne
Published: April 2011

The hypothesis tested was that the hemodynamic consequence of partial hepatectomy (PHX) triggers the cascade of events that leads to liver regeneration. After PHX, all the portal flow must go through the remaining vascular bed, thus producing increased shear stress and release of nitric oxide (NO), which then initiates the next stages of the regeneration process. As an index of triggering of the regeneration cascade, we used an in vitro bioassay detecting the appearance of proliferating factors (PFs; various growth factors, cytokines, and hormones) in plasma 4 h after two-thirds PHX in rats. PF levels, assessed using proliferation of cultured hepatocytes, were elevated in two-thirds PHX rats, fully blocked by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), and restored by L-arginine. L-NAME inhibited liver weight restoration at 48 h but resulted in high mortality. L-NAME lacked toxic effects in non-PHX rats. NO was directly antiproliferative on cultured cells, suggesting that the proliferative effect of NO in vivo was secondary to the activation of other proliferative stimuli. The data support the hypothesis that vascular shear stress induced release of NO following PHX serves as a primary trigger to initiate the regeneration process.Key words: shear stress, portal blood flow, hyperplasia, hepatic partial hepatectomy.
Vagal blockade does not prevent adrenocorticotropin, cortisol, and cardiopulmonary responses to thromboxane A2
Authors: Cudd Timothy A
Published: April 2011

Previously, we reported that thromboxane A2 (TxA2) mediates heart rate, adrenocorticotropin (ACTH), cortisol, and blood gas responses, although the specific site of action was not identified. In the present study, we interrupted vagal nervous transmission in chronically instrumented conscious sheep and infused the TxA2 mimetic U46619 or saline into the carotid artery or U46619 into the vena cava to determine whether TxA2 acts at vagal afferent nerves. Heart rate increased in all three groups during vagal blockade, and responses were not different between groups. Carotid artery and intravenous infusions of U46619 resulted in an increase in blood pressure, but responses were not different between groups. PaO2 decreased in response to vagal blockade in all groups, and responses were not different among groups. Arterial pH increased and PaCO2 decreased during vagal blockade in response to carotid artery U46619 infusions but not in response to vagal blockade alone or combined with carotid artery saline or intravenous U46619. ACTH, cortisol, and hematocrit increased significantly in response to carotid artery infusions of U46619 during vagal blockade but not in response to carotid artery saline or intravenous U46619 infusions. In summary, carotid artery infusions of TxA2 mimetic result in ACTH, cortisol, PaCO2, pHa, and hematocrit responses that are not prevented by vagal blockade. We conclude that these responses are mediated at a site perfused by the carotid vasculature and not at a site innervated by the vagal nerves, findings consistent with the hypothesis that TxA2 acts on the brain to mediate cardiopulmonary and pituitary-adrenal responses.Key words: thromboxane A2, vagus, U46619, adrenocorticotropin, cortisol, prostaglandins, blood pressure, heart rate.
Hypotensive mechanism of [Leu13]motilin in dogs in vivo and in vitro
Authors: Iwai Takeshi , Nakamura Hiroyuki , Takanashi Hisanori , Yogo Kenji , Ozaki Ken-Ichi , Ishizuka Nobuhiko , Asano Tadashi
Published: April 2011

The effects of [Leu13]motilin were examined in vivo after its intravenous administration into anesthetized dogs and in vitro with isolated preparations of canine mesenteric artery. [Leu13]Motilin (0.1-10 nmol·kg-1, i.v.) induced both strong and clustered phasic contractions in the gastric antrum and duodenum. At doses of over 1 nmol·kg-1, [Leu13]motilin also produced transient decreases in arterial blood pressure, left ventricular pressure, maximum rate of rise of left ventricular pressure, and total peripheral resistance, and an increase in aortic blood flow and heart rate. A selective motilin antagonist, GM-109 (Phe-cyclo[Lys-Tyr(3-tBu)-betaAla]betatrifluoroacetate), completely abolished the gastric antrum and duodenal motor responses induced by [Leu13]motilin. In contrast, hypotension induced by [Leu13]motilin (1 nmol·kg-1) was unchanged in the presence of GM-109. In isolated mesenteric artery preparations precontracted with U-46619 (10-7 M), [Leu13]motilin (10-8-10-5 M) induced an endothelium-dependent relaxation, and this was inhibited by a pretreatment with Nomega-nitro-L-arginine, a competitive inhibitor of NO synthase (10-4 M). A high dose (10-4 M) of GM-109 slightly decreased [Leu13]motilin-induced relaxation, and shifted the concentration-response curve of [Leu13]motilin to the right. However, the pA2 value (4.09) of GM-109 for [Leu13]motilin in the present study was conspicuously lower than that previously demonstrated in the rabbit duodenum (7.37). These results suggest that [Leu13]motilin induces hypotension via the endothelial NO-dependent relaxation mechanism and not through the receptor type that causes upper gastrointestinal contractions.Key words: motilin, gastrointestinal motility, hypotension, hemodynamics, anesthetized dog, mesenteric artery, endothelium, nitric oxide.
Coronary endothelium-derived vasodilation during cooling and rewarming of the in situ heart
Authors: Tveita Torkjel , Hevrøy Olav , Refsum Helge , Ytrehus Kirsti
Published: April 2011

The integrity of coronary vascular endothelial vasodilator function during core cooling and rewarming was investigated in a pentobarbital-anesthetized open-chest dog model. Vasodilator response was assessed as the change from baseline blood flow by injecting the endothelial-dependent vasodilator acetylcholine (ACh) (1.0 µg) or the endothelial-independent vasodilator nitroglycerin (NTG) (50 µg) into the left anterior descending (LAD) coronary artery. Change in blood flow was measured using a transit time ultrasonic volume flowmeter technique. During cooling and rewarming LAD blood flow was significantly decreased. After rewarming, aortic pressure was artificially elevated to reach control. This procedure restored heart work (LV-RPP, left ventricular rate pressure product) and coronary perfusion pressure, but LAD blood flow remained lowered. Ability to dilate the vascular bed supplied by LAD, after injections of ACh or NTG, was present both during cooling and rewarming. At 25°C coronary blood flow (LAD) increased from 3 ± 1 to 9 ± 1 mL·min-1 in response to both ACh and NTG. Posthypothermic blood flow increased from 7 ± 1 to 19 ± 2 and 20 ± 3 mL·min-1 in response to ACh and NTG, respectively. Measured as the percent change from baseline LAD blood flow, the response was not significantly different from the one obtained in prehypothermic hearts. In conclusion, coronary vasodilator function, both endothelium dependent and endothelium independent, is present but not maintained at the same level during cooling to 25°C and rewarming. In spite of the deterioration of cardiac function, no selective defect in the endothelium-dependent response was detected, either during hypothermia or after rewarming.Key words: rewarming shock, cold, temperature, coronary blood flow, acetylcholine, nitroglycerin.
Heat shock does not attenuate low-frequency fatigue
Authors: Thomas J A , Noble E G
Published: April 2011

Whole-body hyperthermia or heat shock confers protection to myocardial contractility against reperfusion-induced injury. The purpose of this study was to determine whether heat shock could provide similar protection to skeletal muscle contractility against low-frequency fatigue. Male Sprague-Dawley rats (6 rats/group) were heat shocked at 41.5°C for 15 min either 24 h or 4 days prior to fatiguing stimulation to compare the contractile responses of the plantaris muscle with those of a nonheated group. Both 24 h and 4 days after heat shock, the 72-kDa heat shock protein (HSP72) was elevated above control levels. There were no differences between the heat-shocked and non-heat-shocked animals in measures of contractility prior to fatiguing contractions or in resistance to fatigue. Heat-shock preconditioning did not lead to improved postfatigue force recovery above control responses and, in fact, delayed the recovery of force. This study does not support the use of heat-shock therapy to improve skeletal muscle contractile performance under fatiguing conditions.Key words: heat shock proteins, rat, skeletal muscle, contractile properties, HSP72.
Avian Lankesterella infections in Algonquin Park, Ontario
Authors: Khan R. A. , Desser S. S.
Published: April 2011

During 1966–69 mortality attributed to Lankesterella infections occurred among evening grosbeaks (Hesperiphona vespertina) in Algonquin Park, Ontario. Peak mortality was recorded between mid-June and mid-July in all four years, being highest in 1967. The parasite was subsequently discovered in wild rose-breasted grosbeaks (Pheucticus ludovicianus) and was artificially transmitted to other passerines (though not to a duck) by inoculating infected tissues. Mites from two infected grosbeaks failed to initiate infections when fed to uninfected birds, Isospora oocysts from the feces of grosbeaks were not infective to canaries. The ultrastructure of the parasite in grosbeaks is similar to other eimeriid coccidia. The generic nature of this parasite is discussed in light of recent reports that the species of Lankesterella (= Atoxoplasma) in house sparrows might really be referable to Isospora.
The nymphs of the Nemouridae of Eastern Canada (Insecta: Plecoptera)
Authors: Harper P. P. , Hynes H. B. N.
Published: April 2011

The nymphs of 15 of the 16 species of Nemouridae recorded from Eastern Canada are described and a key for their identification is proposed.
A components study of competition in two cellular slime mold species: Dictyostelium discoideum and Polysphondylium pallidum
Authors: McQueen Donald J.
Published: April 2011

The mechanics of a short-term interspecific competitive situation for two species of cellular slime mold, Dictyostelium discoideum and Polysphondylium pallidum, were assessed experimentally, modelled mathematically, and linked together to form a computer model, the predictions of which were tested. Five major components in the model were exploitation, toxic interference, effect of physical factors or external forces, availability of resources, and number of potential competitors engaged in exploitation and interference. The exploitation component depended upon time required for spore germination, rate and form of amoeba colony expansion, time required for fruiting body production, and rate and form of fruiting body colony expansion.Both species interfered with the other's ability to form fruiting bodies. In mixed cultures, D. discoideum amoebae divided and consumed food between 9° and 27 °C but did not produce fruiting bodies above 24 °C. In mixed cultures, P. pallidum amoebae divided and consumed food between 18° and 37 °C but did not produce fruiting bodies below 24 °C. Temperature altered the parameter values of all subcomponents contributing to exploitation and interference. Numbers altered interference ability. A computer model for predicting area occupied by fruiting bodies of both species was used to run 324 simulations and was accurate in 90.1% of the cases.
A redescription of the nematode Oncholaimus vesicarius (Wieser, 1959) and observations on the pigment spots of this species and of Oncholaimus skawensis Ditlevsen, 1921
Authors: Nelson H. , Webster J. M. , Burr A. H.
Published: April 2011

Oncholaimus vesicarius (Wieser, 1959) n. comb., is described and is differentiated from O. oxyuris (Wieser, 1953) n. comb., by the marked constriction of the body at the anus and by the medial position of the midventral, caudal setose papillae and gubernaculum in the male. It is differentiated from O. steinböcki by the shape and length of the male tail and from O. skawensis by the shorter, stouter tail in both sexes, the very prominent midventral caudal papillae, and the relative proportions of the tail and spicules in the male. Local populations of O. vesicarius and O. skawensis are consistently separated by the color of the anterior pigment spots. The anterior red pigment spots of O. skawensis appear in the late embryonic stage of the unhatched egg and before the appearance of the diffuse brown oesophageal pigment in the oesophageal muscle.
Wildlife foci of Capillaria hepatica infections in Manitoba
Authors: Lubinsky George , Jacobsen B. R. , Baron R. W.
Published: April 2011

Populations of Clethrionomys gapperi and of Peromyscus maniculatus, in which up to 50% of individuals were infected with Capillaria hepatica, were found on the south shore of Lake Manitoba, in the Whiteshell area, and in the region of Lake of the Woods. The potential danger of these foci as sources of subclinical human infections with Capillaria hepatica is pointed out.
Feeding response of the dendrochirote sea cucumber Cucumaria frondosa (Echinodermata: Holothuroidea) to changing food concentrations in the laboratory
Authors: Singh Rabindra , MacDonald Bruce A , Lawton Peter , Thomas Martin LH
Published: April 2011

Sea cucumbers (Cucumaria frondosa) (Echinodermata: Holothuroidea) held in flow-through tanks were exposed to different chloropigment concentrations by manipulating the seston concentration via the use of water filters in the inflow lines and the addition of cultured algae or natural plankton to tanks. The percentage of sea cucumbers open and feeding increased asymptotically as the seston chloropigment concentration increased. Below 50 µg·L-1 the percentage of sea cucumbers with tentacles extended and feeding decreased. The rate at which sea cucumbers inserted their tentacles into their mouths (0.96 ± 0.34 insertion/min (mean ± SD)) increased with increasing seston quality. Cucumaria frondosa fed at faster rates at the higher concentrations. There was a significant positive relationship between the stomach content (amount of chloropigment) of sea cucumbers and the seston chloropigment concentration to which they were exposed (r2 = 0.200, p < 0.001).
Death receptors mediate the adverse effects of febrile-range hyperthermia on the outcome of lipopolysaccharide-induced lung injury
Authors: Lipke Anne B. , Matute-Bello Gustavo , Herrero Raquel , Wong Venus A. , Mongovin Stephen M. , Martin Thomas R.
Published: April 2011

We have shown that febrile-range hyperthermia enhances lung injury and mortality in mice exposed to inhaled LPS and is associated with increased TNF-α receptor activity, suppression of NF-κB activity in vitro, and increased apoptosis of alveolar epithelial cells in vivo. We hypothesized that hyperthermia enhances lung injury and mortality in vivo by a mechanism dependent on TNF receptor signaling. To test this, we exposed mice lacking the TNF-receptor family members TNFR1/R2 or Fas (TNFR1/R2−/−and lpr) to inhaled LPS with or without febrile-range hyperthermia. For comparison, we studied mice lacking IL-1 receptor activity (IL-1R−/−) to determine the role of inflammation on the effect of hyperthermia in vivo. TNFR1/R2−/−and lpr mice were protected from augmented alveolar permeability and mortality associated with hyperthermia, whereas IL-1R−/−mice were susceptible to augmented alveolar permeability but protected from mortality associated with hyperthermia. Hyperthermia decreased pulmonary concentrations of TNF-α and keratinocyte-derived chemokine after LPS in C57BL/6 mice and did not affect pulmonary inflammation but enhanced circulating markers of oxidative injury and nitric oxide metabolites. The data suggest that hyperthermia enhances lung injury by a mechanism that requires death receptor activity and is not directly associated with changes in inflammation mediated by hyperthermia. In addition, hyperthermia appears to enhance mortality by generating a systemic inflammatory response and not by a mechanism directly associated with respiratory failure. Finally, we observed that exposure to febrile-range hyperthermia converts a modest, survivable model of lung injury into a fatal syndrome associated with oxidative and nitrosative stress, similar to the systemic inflammatory response syndrome.
Neurokinin-neurotrophin interactions in airway smooth muscle
Authors: Meuchel Lucas W. , Stewart Alecia , Smelter Dan F. , Abcejo Amard J. , Thompson Michael A. , Zaidi Syed I. A. , Martin Richard J. , Prakash Y. S.
Published: April 2011

Neurally derived tachykinins such as substance P (SP) play a key role in modulating airway contractility (especially with inflammation). Separately, the neurotrophin brain-derived neurotrophic factor (BDNF; potentially derived from nerves as well as airway smooth muscle; ASM) and its tropomyosin-related kinase receptor, TrkB, are involved in enhanced airway contractility. In this study, we hypothesized that neurokinins and neurotrophins are linked in enhancing intracellular Ca2+ concentration ([Ca2+]i) regulation in ASM. In rat ASM cells, 24 h exposure to 10 nM SP significantly increased BDNF and TrkB expression ( P < 0.05). Furthermore, [Ca2+]i responses to 1 μM ACh as well as BDNF (30 min) effects on [Ca2+]i regulation were enhanced by prior SP exposure, largely via increased Ca2+ influx ( P < 0.05). The enhancing effect of SP on BDNF signaling was blunted by the neurokinin-2 receptor antagonist MEN-10376 (1 μM, P < 0.05) to a greater extent than the neurokinin-1 receptor antagonist RP-67580 (5 nM). Chelation of extracellular BDNF (chimeric TrkB-Fc; 1 μg/ml), as well as tyrosine kinase inhibition (100 nM K252a), substantially blunted SP effects ( P < 0.05). Overnight (24 h) exposure of ASM cells to 50% oxygen increased BDNF and TrkB expression and potentiated both SP- and BDNF-induced enhancement of [Ca2+]i ( P < 0.05). These results suggest a novel interaction between SP and BDNF in regulating agonist-induced [Ca2+]i regulation in ASM. The autocrine mechanism we present here represents a new area in the development of bronchoconstrictive reflex response and airway hyperreactive disorders.
Targeting the p53 Pathway in Retinoblastoma with Subconjunctival Nutlin-3a
Authors: Brennan Rachel C. , Federico Sara , Bradley Cori , Zhang Jiakun , Flores-Otero Jacqueline , Wilson Matthew , Stewart Clinton , Zhu Fangyi , Guy Kip , Dyer Michael A.
Published: April 2011

Retinoblastoma is a rare childhood cancer of the retina that begins in utero and is diagnosed in the first years of life. The goals of retinoblastoma treatment are ocular salvage, vision preservation, and reduction of short- and long-term side effects without risking mortality because of tumor dissemination. To identify better chemotherapeutic combinations for the treatment of retinoblastoma, several groups have developed genetic mouse models and orthotopic xenograft models of human retinoblastoma for preclinical testing. Previous studies have implicated the MDMX protein in the suppression of the p53 pathway in retinoblastoma and shown that the MDM2/MDMX antagonist, Nutlin-3a, can efficiently induce p53-mediated cell death in retinoblastoma cell lines. However, Nutlin-3a cannot be administered systemically to treat retinoblastoma, because it has poor penetration across the blood–ocular barrier. Therefore, we developed an ocular formulation of Nutlin-3a, Nutlin-3aOC, and tested the pharmacokinetics and efficacy of this new formulation in genetic and human retinoblastoma orthotopic xenograft models of retinoblastoma. Here, we show that Nutlin-3aOC specifically and efficiently targets the p53 pathway and that the combination of Nutlin-3aOC with systemic topotecan is a significantly better treatment for retinoblastoma than currently used chemotherapy in human orthotopic xenografts. Our studies provide a new standardized approach to evaluate and prioritize novel agents for incorporation into future clinical trials for retinoblastoma. Cancer Res; 71(12); 4205–13. ©2011 AACR.
Cost Effectiveness of Warfarin Versus Aspirin in Patients Older Than 75 Years With Atrial Fibrillation
Authors: Jowett Sue , Bryan Stirling , Mant Jonathan , Fletcher Kate , Roalfe Andrea , Fitzmaurice David , Lip Gregory Y.H. , Hobbs F.D. Richard
Published: April 2011

Background and Purpose—

Oral anticoagulants are effective at reducing stroke compared with aspirin in atrial fibrillation patients older than 75 years. Although the benefits of reduced stroke risk outweigh the risks of bleeding, the cost effectiveness of warfarin in this patient population has not yet been established.

Methods—

An economic evaluation was conducted alongside a randomized, controlled trial; 973 patients ≥75 years of age with atrial fibrillation were recruited from primary care and randomly assigned to either take warfarin or aspirin. Follow-up was for a mean of 2.7 years. Costs of thrombotic and hemorrhagic events, anticoagulation clinic visits, and primary care utilization were determined. Clinical benefits were expressed in terms of a primary event avoided: fatal/nonfatal disabling stroke, intracranial hemorrhage, or systemic embolism. A cost-utility analysis was performed using quality-adjusted life years as the benefit measure.

Results—

Total costs over 4 years were lower in the warfarin group (difference, −£165; 95% CI, −£452–£89), primarily driven by the difference in primary event costs. The primary event rate over 4 years was lower in the warfarin group (0.049 versus 0.099), and the quality-adjusted life years score was higher (difference, 0.02; 95% CI, −0.07–0.11). With lower costs and a higher quality-adjusted life years score, warfarin is the dominant treatment, but the differences in both costs and effects are small.

Conclusions—

Warfarin is cost-effective compared with aspirin in atrial fibrillation patients age ≥75 years. These data support the anticoagulant therapy option in this high-risk patient population. However, the small differences in costs and effects indicate the importance of exploring patient preferences.
A Topographic Study of the Evolution of the MR DWI/PWI Mismatch Pattern and Its Clinical Impact
Authors: Ogata Toshiyasu , Nagakane Yoshinari , Christensen Soren , Ma Henry , Campbell Bruce C.V. , Churilov Leonid , Olivot Jean-Marc , Desmond Patricia M. , Albers Gregory W. , Davis Stephen M. , Donnan Geoffrey A.
Published: April 2011

Background and Purpose—

The ischemic penumbra may be classical, with complete annular configuration around the infarct core, or nonclassical with a more fragmented pattern. We tested the hypotheses that these penumbral patterns may: be associated with specific predictive factors, influence infarct growth and clinical outcome, and influence the effect of tissue plasminogen activator (t-PA).

Methods—

Using the EPITHET/DEFUSE data set, in which patients received alteplase or placebo 3 to 6 hours poststroke, perfusion-weighted imaging and diffusion-weighted imaging images were analyzed. These mismatch patterns were defined as “classical” or “nonclassical.” Multivariate analysis was used to identify variables associated with mismatch patterns, the effect of t-PA, as well as the relationship between mismatch patterns, infarct growth, and clinical outcomes.

Results—

We included 158 patients (median age, 74 years; median National Institute of Health Stroke Scale score, 12). Multivariate analysis indicated that the factors associated with classical mismatch pattern type were large mismatch volume (
P
<0.001) and cortical infarct location (
P
=0.036). Infarct growth, clinical outcome, and the efficacy of t-PA were not statistically different between patterns.

Conclusions—

Coregistered mismatch volume and cortical location of infarction were the important factors associated with presence of the classical mismatch pattern. The lack of effect of the type of mismatch patterns on infarct growth, clinical outcomes, or the benefit of t-PA would suggest that mismatch topography is less important during the hyperacute phase of ischemic stroke than during subacute phase.
Effects of Continuous Hypertonic Saline Infusion on Perihemorrhagic Edema Evolution
Authors: Wagner Ingrid , Hauer Eva-Maria , Staykov Dimitre , Volbers Bastian , Dörfler Arnd , Schwab Stefan , Bardutzky Jürgen
Published: April 2011

Background and Purpose—

Mass effect of hematoma and the associated perihematomal edema are commonly responsible for neurological deterioration after intracerebral hemorrhage. Efficacy of surgical and medical therapy is limited. We studied the effect of early continuous hypertonic saline infusion on development of perihematomal edema after severe spontaneous supratentorial hemorrhage.

Methods—

Patients with spontaneous lobar and basal ganglia/thalamic bleeding >30 mL (n=26) were treated with early (<72 hours) continuous hypertonic saline infusion (3%) to achieve sodium of 145 to 155 mmol/L and osmolality of 310 to 320 mOsmol/kg. Evolution of absolute edema volume and relative edema volume (ratio absolute edema volume/initial hematoma volume) was assessed on repeated cranial CT and compared to historical patients (n=64) identified on database with hematoma >30 mL.

Results—

In the treatment group, absolute edema volume was significant smaller between day 8 and day 14 (
P
absolute edema volume
= 0.04) and relative edema volume was significant smaller between day 2 and day 14 (
P
relative edema volume
=0.02). Intracranial pressure crisis (>20 mm Hg for >20 minutes or new anisocoria) occurred less frequently in the treatment group (12 versus 56;
P
=0.048). In-hospital mortality was 3 (11.5%) in the hypertonic saline group and 16 (25%) in the control group (
P
=0.078). Side effects theoretically associated with hypertonic saline including cardiac arrhythmia and acute heart and renal failure occurred in both groups to a similar extent.

Conclusions—

Early and continuous infusion of hypertonic saline in patients with severe spontaneous intracerebral hemorrhage was feasible and safe. The beneficial effect of this treatment regimen on edema evolution and outcome has to be demonstrated in a controlled trial.
MCP1 haplotypes associated with protection from pulmonary tuberculosis
Authors: Intemann Christopher D , Thye Thorsten , Förster Birgit , Owusu-Dabo Ellis , Gyapong John , Horstmann Rolf D , Meyer Christian G
Published: April 2011

Background

The monocyte chemoattractant protein 1 (MCP-1) is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB) case-control study group, associations of theMCP1-362C and theMCP1-2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate theMCP1gene in order to determine causal variants or haplotypes genetically and functionally.

Results

A 14 base-pair deletion in the firstMCP1intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, Pcorrected= 0.00098). Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, Pnominal= 0.00002; adjusted Pglobal= 0.0028). In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying theMCP1mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006). The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB.

Conclusions

In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does theMCP1-362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91). Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the variant at position -2581 in the Ghanaian population studied.
The distal end of porcine chromosome 6p is involved in the regulation of skatole levels in boars
Authors: Ramos António M , Duijvesteijn Naomi , Knol Egbert F , Merks Jan WM , Bovenhuis Henk , Crooijmans Richard PMA , Groenen Martien AM , Harlizius Barbara
Published: April 2011

Background

Boar taint is an unpleasant condition of pork, mainly due to the accumulation of androstenone and skatole in male pigs at onset of puberty. This condition is the cause of considerable economic losses in the pig industry and the most common practice to control it is to castrate male piglets. Because of the economic and animal welfare concerns there is interest in developing genetic markers that could be used in selection schemes to decrease the incidence of boar taint. The Porcine 60 K SNP Beadchip was used to genotype 891 pigs from a composite Duroc sire line, for which skatole levels in fat had been collected.

Results

The genome-wide association study revealed that 16 SNPs (single nucleotide polymorphisms) located on the proximal region of chromosome 6 were significantly associated with skatole levels. These SNPs are grouped in three separate clusters located in the initial 6 Mb region of chromosome 6. The differences observed between the homozygote genotypes for SNPs in the three clusters were substantial, including a difference of 102.8 ng/g skatole in melted fat between the homozygotes for the ALGA0107039 marker. Single SNPs explain up to 22% of the phenotypic variance. No obvious candidate genes could be pinpointed in the region, which may be due to the need of further annotation of the pig genome.

Conclusions

This study demonstrated new SNP markers significantly associated with skatole levels in the distal region of chromosome 6p. These markers defined three independent clusters in the region, which contain a low number of protein-coding genes. The considerable differences observed between the homozygous genotypes for several SNPs may be used in future selection schemes to reduce skatole levels in pigs
Double auricles of the right atrium: a unique anatomic deformity
Authors: Tagarakis Georgios I , Karangelis Dimos , Daskalopoulos Marios E , Papadopoulos Dimitrios , Koufakis Theocharis , Karantzis Ioannis , Lampoura Stefania S , Chlapoutakis Serapheim , Tsilimingas Nikolaos B
Published: April 2011

Background

Anatomic deviations, especially those detected during the course of an operation, are medically intriguing, as they raise concerns about their clinical significance and putative complications.

Case presentation

We present, to our knowledge, for the first time a case of an anatomic deviation in the form of a second right atrial auricle in a 70 year-old, coronary bypass-operated male Caucasian patient of Greek origin. No complications were noted intra-or postoperatively.

Conclusions

A second right atrial auricle was found intraoperatively, without causing any clinical complications, or obstructing the normal course of a surgical procedure.