bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protecting murine hearts from ischaemia–reperfusion using selective inhibitors of adenosine metabolism
Authors: Willems Laura , Headrick John P 
Published: March 2005

SUMMARY1. By selectively modifying adenosine metabolism via adenosine deaminase or adenosine kinase inhibitors, it may be possible to enhance the receptor‐mediated protective actions of adenosine in a site‐ and event‐specific fashion.2. We characterized cardioprotective actions of the adenosine deaminase inhibitor erythro‐2‐(2‐hydroxy‐3‐non‐yl)adenine (EHNA) and the adenosine kinase inhibitor iodotubercidin in C57/Bl6 mouse hearts subjected to 20 min global normothermic ischaemia and 40 min reperfusion.3. Ventricular pressure development only recovered to 45 ± 2% of baseline levels (67 ± 5 mmHg) in untreated hearts, with sustained and pronounced diastolic contracture (25 ± 2 mmHg). Treatment with 20 µmol/L EHNA increased recovery of ventricular pressure (107 ± 9 mmHg), reduced postischaemic diastolic pressure (13 ± 1 mmHg) and reduced loss of lactate dehydrogenase (LDH; an indicator of necrotic damage) by 50% (9 ± 2 vs 19 ± 2 IU/g). Adenosine kinase inhibition with 10 µmol/L iodotubercidin also improved pressure development (to 100 ± 8 mmHg) and reduced LDH efflux (5 ± 2 IU/g).4. Protective actions were mimicked by adenosine and inhibited by adenosine receptor antagonism (50 µmol/L 8‐ρ‐sulfophenyltheophylline) and mitochondrial KATP channel inhibition (50 µmol/L 5‐hydroxydecanoate).5. Coinfusion of the inhibitors, ‘trapping’ formed adenosine, failed to exert protection and, in some instances, was detrimental. Although substantial benefit was gained by these agents in hearts from young animals, neither inhibitor was effective in ‘aged’ hearts (18 months).6. Our data demonstrate that adenosine deaminase or kinase inhibition substantially limits injury during ischaemia–reperfusion. Protection involves adenosine receptor activation. However, cardioprotection via either enzyme inhibitor requires an alternative purine‐salvage pathway to be functional and was reduced in aged hearts known to be increasingly susceptible to ischaemic damage.
Inhibitory effect of sildenafil on rat duodenal contractility In vitro: Putative cGMP involvement
Authors: Araújo Paula Vasconcelos , Clemente Cristiano Magalhães , Da Graça José Ronaldo Vasconcelos , Rola Francisco Hélio , De Oliveira Ricardo Brandt , Dos Santos Armênio Aguiar , Magalhães Pedro Jorge Caldas 
Published: March 2005

SUMMARY1. Sildenafil citrate (Viagra™; Pfizer, Sandwich, Kent, UK), a phosphodiesterase 5 inhibitor, rises cGMP levels in smooth muscle cells. It relaxes both vascular and visceral smooth muscle. In order to assess the intestinal effects of sildenafil, we decided to investigate its actions on rat duodenal motor activity in vitro.2. In isolated duodenal segments maintained in Tyrode's solution, sildenafil exhibited a concentration‐dependent antispasmodic effect on acetylcholine (ACh)‐induced phasic contractions, with an IC50 value of 26.7 µmol/L (95% confidence interval (CI) 2.0–55.3 µmol/L).3. Sildenafil also relaxed the carbamylcholine (CCh)‐induced sustained contraction with an IC50 of 16.2 µmol/L (95% CI 9.5–27.6 µmol/L). Sildenafil produced significant additional relaxation of 25.2 ± 8.1% of the CCh‐induced contraction, beyond basal tone.4. Sildenafil reduced the amplitude of spontaneous duodenal contractions with an EC50 of 9.6 µmol/L (95% CI 5.7–16.2 µmol/L). This effect was significantly more potent than the effects of zaprinast and papaverine, which also reduced duodenal contractions with EC50 values of 91.6 µmol/L (95% CI 46.0–182.2 µmol/L) and 78.5 µmol/L (95% CI 37.1–166.3 µmol/L), respectively.5. In preparations treated previously with methylene blue (10 μmol/L) or 1H‐[1,2,4]oxadiazolo(4,3‐a)quinoxalin‐1‐one (ODQ; 10 µmol/L), the EC50 values for the sildenafil effect were significantly increased to 39.0 µmol/L (95% CI 23.9–63.4 µmol/L) and 43.8 µmol/L (95% CI 24.5–78.3 µmol/L), respectively. These values were significantly greater than those obtained with sildenafil alone.6. In conclusion, sildenafil has myorelaxant and antispasmodic effects on rat duodenal segments in vitro. The contractile inhibitory effect of sildenafil on rat isolated duodenum is probably due to intracellular cGMP accumulation as a result of its decreased degradation.
Role of heme oxygenase/carbon monoxide pathway on the vascular response to noradrenaline in portal hypertensive rats
Authors: Erario MA , Gonzales S , Romay S , Eizayaga FX , Castro JL , Lemberg A , Tomaro ML 
Published: March 2005

SUMMARY1. Portal hypertension (PH), a major syndrome in cirrhosis, producing hyperdynamic splanchnic circulation and hyperaemia. In order to elucidate the contribution of heme oxygenase to the vascular hyporeactivity, we assessed the activity of heme oxygenase‐1 (HO‐1), measured the in vivo pressure response to noradrenaline (NA) and investigated the effects of blocking the carbon monoxide (CO) and nitric oxide (NO) pathways in a prehepatic model of PH in rats.2. Portal hypertension was induced by partial portal vein ligation (PPVL). Noradrenaline was injected intravenously. Liver, spleen and mesentery homogenates were prepared for measurement of HO‐1 activity and expression. Four groups of rats were used: (i) a sham group; (ii) a PPVL group; (iii) a sham group pretreated with Zn‐protoporphyrin IX (ZnPPIX); and (iv) a PPVL group pretreated with ZnPPIX. Each group was studied before and after treatment with the NO synthase inhibitor NG‐nitro‐l‐arginine methyl ester (l‐NAME).3. For basal pressures and the pressure response to NA, inhibition of CO and NO pathways by ZnPPIX and l‐NAME, respectively, produced an increase in mean arterial pressure (MAP) in sham‐operated and in PH rats. Similarly, when both inhibitors were used together in either sham or PPVL rats, a greater increase in MAP was observed.4. These results, together with the increased HO‐1 activity and expression only in the PH group, have led us to suggest that the heme oxygenase/CO pathway is involved in the vascular response to NA in PH rats.
Effect of pregnancy on the roles of nitric oxide and prostaglandins in 5‐hydroxytryptamine‐induced contractions in rat isolated thoracic and abdominal aorta
Authors: Bobadilla L Rosa A , Pérez‐Alvarez Víctor , Bracho Valdés Ismael , López‐Sanchez Pedro 
Published: March 2005

SUMMARY1. Vascular resistance and sensitivity to circulating pressor and vasoconstrictor substances are blunted during pregnancy. This has been attributed mainly to an increased production of endothelium‐derived mediators. The aim of the present study was to determine whether pregnancy changes the relative participation of nitric oxide (NO) and prostaglandins (PG) in the modulation of the contractile response to 5‐hydroxytryptamine (5‐HT) in two anatomically distint segments of the rat aorta.2. Full concentration–response curves to 5‐HT were obtained in isolated rings from the thoracic and abdominal portion of the aorta from pregnant and non‐pregnant rats in the presence and absence of the NO synthase (NOS) inhibitor NG‐nitro‐l‐arginine methyl ester (l‐NAME; 10 µmol/L) or the PG synthesis inhibitor indomethacin (10 µmol/L). Cyclo‐oxygenase (COX)‐1, COX‐2 and endothelial (e) NOS protein expression were determined in the same tissues by immunoblot.3. The effects of pregnancy were accentuated in the abdominal compared with the thoracic aorta. In addition, the relative participation of the NO and PG pathways seems to be changed during pregnancy. Although NO seems to be the mediator mainly responsible for the effect of pregnancy in the thoracic aorta, our results suggest a complex interaction between NO and PG in the abdominal aorta. Indomethacin significantly reduced the contractile response of both segments of the aorta, whereas expression of COX‐1, COX‐2 and eNOS were increased only in the abdominal segment of pregnant animals.4. These results show that the effect of pregnancy is not homogeneous along the aorta. There seems to be a mutual interaction between PG and NO in the abdominal, but not in the thoracic, aorta from pregnant rats: the role of NO becomes evident in the absence of vasodilatory PG, whereas the participation of the latter increases in the absence of NO working as a compensatory mechanism.
Acute effects of hydrocortisone on plasma nitrate/nitrite activity and forearm vasodilator responsiveness in normal human subjects
Authors: Williamson Paula M , Kohlhagen Johanna L , Mangos George J , Whitworth Judith A , Kelly John J 
Published: March 2005

SUMMARY1. The aim of the present study was to examine the acute effects of cortisol infusion on plasma nitrate/nitrite (NO) activity and forearm vascular responsiveness to acetylcholine.2. We performed two randomized, placebo‐controlled, cross‐over studies. Study A examined the effects of intravenous hydrocortisone (200 mg over a 3 h period) on blood pressure (BP) and plasma NO activity in six healthy male volunteers. Study B examined the effects of intra‐arterial hydrocortisone on cholinergic vasodilator responsiveness in six healthy male volunteers. Vasodilator responsiveness was measured by bilateral strain gauge plethysmography.3. In study A, there was no significant change in BP during the hydrocortisone infusion. Comparing values obtained following 180 min infusion of hydrocortisone and control, there were significant increases in plasma cortisol (3441 ± 342 vs 209 ± 29 nmol/L, respectively; P < 0.001) and glucose (5.7 ± 0.2 vs 4.6 ± 0.2 mmol/L, respectively; P < 0.05) and a reduction in plasma renin concentration (PRC) (8.1 ± 1.2 vs 11.0 ± 1.8 pg/mL, respectively; P < 0.05) following hydrocortisone infusion. However, there were no significant changes in either plasma NO or in the endogenous NO synthase inhibitors asymmetrical and symmetrical dimethylarginine.4. In study B, there was no significant change in BP or in cholinergic vasodilator responsiveness during the hydrocortisone infusion.5. Short‐term cortisol infusions do not alter biochemical or physiological markers of NO activity. If cortisol‐induced hypertension is mediated by suppression of NO activity in humans, it seems likely that these changes take more than 3 h to become detectable.
Experimental and clinical study of the combined effect of arterial stiffness and heart rate on pulse pressure: Differences between central and peripheral arteries
Authors: Papaioannou Theodoros G , Protogerou Athanassios , Papamichael Christos , Mathioulakis Dimitrios , Tsangaris Sokratis , Karatzis Emmanouil , Toumanidis Savvas , Zakopoulos Nicolaos , Lekakis John 
Published: March 2005

SUMMARY1. Pulse pressure (PP) constitutes an independent predictor of cardiovascular events and mortality in various populations. Heart rate (HR) and arterial stiffness, in addition to their independent predictive value for cardiovascular complications, seem to interact with regard to the modification of PP. The aim of the present study was to investigate the association of PP with HR under different levels of arterial compliance (AC), revealing their synergistic effects.2. Seventy‐one normotensive and untreated hypertensive subjects were examined. Arterial compliance was measured by the ‘area’ method, whereas central blood pressures and wave reflections were evaluated using the Sphygmocor® system (AtCor Medical, Sydney, NSW, Australia). A hydraulic Windkessel model was also used to evaluate the independent effect of HR and AC on PP. Peripheral PP was associated only with mean pressure and AC. In contrast, central PP was further related to HR (20 b.p.m. decrease in HR resulted in central PP augmentation by 5.6 mmHg) regardless of mean pressure, stroke volume, age and gender. However, this association was statistically significant only for subjects with lower AC (< 1.1 mL/mmHg) and not for those with more compliant arteries. These findings are also in accordance with the experimental data.3. Aortic PP is affected to a greater degree by HR changes compared with peripheral PP. This response was observed only at high levels of arterial stiffness.4. The present study provides the first evidence regarding the combined effect of AC and HR on aortic PP, which may lead to larger clinical or epidemiological studies aiming to optimization of drug treatment and to a possible reduction of cardiovascular risk.
Effects of 15‐deoxy‐Δ12,14‐prostaglandin J2 on the expression of Toll‐like receptor 4 and 2 in the murine lung in the presence of lipopolysaccharide
Authors: Inoue Ken‐ichiro , Takano Hirohisa , Yanagisawa Rie , Ichinose Takamichi , Sadakane Kaori , Yoshino Shin , Yamaki Kouya , Uchiyama Kazuhiko , Yoshikawa Toshikazu 
Published: March 2005

Summary1. Previously, we have demonstrated that 15‐deoxy‐Δ12,14‐prostaglandin J2 (15d‐PGJ2) enhances acute lung injury induced by lipopolysaccharide (LPS) in mice. The enhancement in acute lung injury by 15d‐PGJ2 was concomitant with the enhanced expression of several pro‐inflammatory cytokines in the lung. However, other underlying mechanisms of this enhancement remain to be elucidated. The present study investigated the effects of 15d‐PGJ2 on the expression of Toll‐like receptor (TLR) 4 and 2 in the lung in the absence or presence of LPS.2. In the present study, ICR mice were divided into four experimental groups that received (intratracheally) vehicle, LPS (125 μg/kg), 15d‐PGJ2 (1 mg/kg) or 15d‐PGJ2 + LPS. The mRNA expression of both TLR4 and 2 in the lung was evaluated 4 h after intratracheal administration.3. 15‐Deoxy‐Δ12,14‐prostaglandin J2 enhanced the mRNA expression of both TLR4 and 2 in the presence of LPS.4. These results suggest that the enhancing effects of 15d‐PGJ2 on LPS‐induced acute lung injury may be explained, at least in part, by its effect on the lung expression of TLR4 and 2.
Inhibition of calcineurin increases monocarboxylate transporters 1 and 4 protein and glycolytic enzyme activities in rat soleus muscle
Authors: Suwa Masataka , Nakano Hiroshi , Kumagai Shuzo 
Published: March 2005

SUMMARY1. The present study was designed to examine the role of calcineurin in muscle metabolic components by the administration of the specific calcineurin inhibitor cyclosporine A (CsA) to rats.2. Male Wistar rats were divided into either a CsA‐treated group (CT) or a vehicle‐treated group (VT). Cyclosporine A was administered subcutaneously to rats at a rate of 25 mg/kg bodyweight per day for 10 successive days. Thereafter, changes in muscle enzyme activities and glucose transporter (GLUT)‐4 and monocarboxylate transporter (MCT)‐1 and MCT‐4 proteins in the slow‐twitch soleus and fast‐twitch extensor digitorum longus (EDL) muscles were examined.3. There was a significant increase in MCT‐1 and MCT‐4 proteins in the soleus muscle in the CT group, but not in the EDL muscle. The activities of hexokinase, pyruvate kinase and lactate dehydrogenase in the soleus muscle also increased significantly in the CT group, but a similar increase in enzyme activity was not seen in EDL muscle. The activities of citrate synthase or malate dehydrogenase and the GLUT‐4 protein content were not altered by CsA treatment in either the soleus or EDL muscles.4. These results seem to imply that calcineurin negatively regulates the components of glucose/lactate metabolism, except for GLUT‐4, especially in slow‐twitch muscle.
Oxidized low‐density lipoprotein‐induced apoptosis is attenuated by insulin‐activated phosphatidylinositol 3‐kinase/Akt through p38 mitogen‐activated protein kinase
Authors: Nihei Shun‐ichi , Yamashita Kazuhito , Tasaki Hiromi , Ozumi Kiyoshi , Nakashima Yasuhide 
Published: March 2005

SUMMARY1. The aim of the present study was to investigate whether p38 mitogen‐activated protein kinase (p38 MAPK) is involved in oxidized low‐density lipoprotein (oxLDL)‐induced apoptosis of human umbilical vein endothelial cells (HUVECs). We also sought to determine whether this apoptosis is regulated by the phosphatidylinositol 3‐kinase (PI3K)/Akt pathway.2. Low‐density lipoprotein was oxidized with CuSO4 and used as oxLDL. Using HUVEC, we determined whether LDL/oxLDL induces apoptosis by DNA fragmentation and the cell cycle distribution (SubG1 method). The mechanism and activation of p38 MAPK and Akt were determined by western blot analysis.3. The results showed that oxLDL induced DNA fragmentation, whereas cell cycle distribution showed that it also significantly increased the rate of cell death compared with the LDL group. SB203580 significantly inhibited cell death induced by oxLDL, as did the administration of insulin. Western blot analysis showed the activation of p38 MAPK by oxLDL, but not with LDL. It was found that Akt was activated in the presence of insulin. In the presence of either SB203580 or insulin, activation of p38 MAPK was significantly inhibited compared with stimulation by oxLDL alone. However, application of both insulin and wortmannin resulted in no significant difference compared with HUVEC stimulated by oxLDL only.4. The results showed that apoptosis in HUVEC can be induced by oxLDL and involves p38 MAPK. It was also demonstrated that insulin inhibited oxLDL‐induced apoptosis and may inhibit the activation of p38 MAPK through the PI3K/Akt pathway.
Embryonic and larval development of Thai Pangas (Pangasius sutchi Fowler, 1937)
Authors: Islam Asiful 
Published: March 2005

The embryonic and larval development of Thai pangas was investigated during peak (May–July 1995) and late spawning (August–October 1995) periods. The fertilized eggs are adhesive and spherical with a yellowish or greenish‐brown egg capsule. The yolk sac is yellowish‐brown in color and 1.20–1.80 mm in diameter. Nine hours post‐fertilization, the first cleavage stage, embryonic shield, head, tail region, neural grooves and somites were evident. The incubation period ranges from 24–36 h at a temperature of 20–30°C. The newly hatched larvae are quite transparent and light yellowish in color with a body length of 2.98–3.10 mm. Eye pigments appear and the heart starts to work within 12–14 h of hatching. In 1‐day‐old pro‐larvae, the mouth becomes well developed; barbules are elongated, prominent and look like tiny threads. The yolk sac is fairly well absorbed and the palatine teeth are fully developed during the 3 day pro‐larval stage. At the end of 12 days of larval development, the stomach becomes functional and aerial respiration starts. After 2 weeks, the young fry is well‐developed, and is of an adult appearance, that is, measuring up to 13.56 mm in length.
Gamete fusion and cytokinesis preceding zygote establishment in the sexual process of Dictyostelium discoideum
Authors: Ishida Kentaro , Hata Toshihiro , Urushihara Hideko 
Published: March 2005

Cells of Dictyostelium discoideum become sexually mature under submerged and dark conditions, and fuse with opposite mating‐type cells to form zygote giant cells, which gather surrounding cells and finally develop into dormant structures called macrocysts. In the present study, we found that the multinuclear fused cells formed during this process frequently underwent cytokinesis driven by random local movements. The split cells were capable of re‐fusion, and repeated cytokinesis. These radical behaviors continued until the extensive cell aggregation started around the giant cells. Thus, gamete fusion and initiation of zygote development do not coincide in the mating of D. discoideum. Analyses by confocal microscopy and flow cytometry indicated that the cessation of the random movement followed pronuclear fusion, and that microtubule organizing centers (MTOC), abundant in the fused cells at the beginning, gradually decreased and only one of them remained within the developed macrocyst. Some of the genes known to control cell movement, such as rasGEFB and rasS, increased shortly before the cessation of repeated fusion‐cytokinesis and initiation of phagocytosis. These results suggest that the sequential molecular events are necessary in D. discoideum after gamete fusion to establish a new individuality of zygotes.
Management of femoral artery thrombosis in an immature dog
Authors: Tater Kathy C. , Drellich Sharon , Beck Kathy 
Published: March 2005

AbstractObjective:To report a case of femoral artery thrombosis and its medical management in a young dog.Case summary:A 13‐week‐old, female Boxer puppy presented with hind limb paralysis after an abdominal crush injury. A left femoral artery thrombus was identified on ultrasound. No spinal trauma was visualized in imaging studies. Clinical management of arterial thrombosis in a 13‐week‐old puppy with streptokinase and dalteparin therapy is described.New or unique information provided:This paper describes an unusual presentation of arterial thrombosis. The medical management with streptokinase and dalteparin is also out of the ordinary. Images that document the development of compensatory circulation around the thrombosed vessel are included. Additionally, this paper also documents the altered development that occurred in this immature dog after the thrombotic event.
Testing Agency Theory with Entrepreneur Effort and Wealth
Authors: BITLER MARIANNE P. , MOSKOWITZ TOBIAS J. , VISSING‐JØRGENSEN ANNETTE 
Published: March 2005

ABSTRACTWe develop a principal‐agent model in an entrepreneurial setting and test the model's predictions using unique data on entrepreneurial effort and wealth in privately held firms. Accounting for unobserved firm heterogeneity using instrumental‐variables techniques, we find that entrepreneurial ownership shares increase with outside wealth and decrease with firm risk; effort increases with ownership; and effort increases firm performance. The magnitude of the effects in the cross‐section of firms suggests that agency costs may help explain why entrepreneurs concentrate large fractions of their wealth in firm equity.
Entrepreneurial Spawning: Public Corporations and the Genesis of New Ventures, 1986 to 1999
Authors: GOMPERS PAUL , LERNER JOSH , SCHARFSTEIN DAVID 
Published: March 2005

ABSTRACTWe examine two views of the creation of venture‐backed start‐ups, or “entrepreneurial spawning.” In one, young firms prepare employees for entrepreneurship, educating them about the process, and exposing them to relevant networks. In the other, individuals become entrepreneurs when large bureaucratic employers do not fund their ideas. Controlling for firm size, patents, and industry, the most prolific spawners are originally venture‐backed companies located in Silicon Valley and Massachusetts. Undiversified firms spawn more firms. Silicon Valley, Massachusetts, and originally venture‐backed firms typically spawn firms only peripherally related to their core businesses. Overall, entrepreneurial learning and networks appear important in creating venture‐backed firms.
Liquidity Shortages and Banking Crises
Authors: DIAMOND DOUGLAS W. , RAJAN RAGHURAM G. 
Published: March 2005

ABSTRACTWe show in this article that bank failures can be contagious. Unlike earlier work where contagion stems from depositor panics or contractual links between banks, we argue that bank failures can shrink the common pool of liquidity, creating, or exacerbating aggregate liquidity shortages. This could lead to a contagion of failures and a total meltdown of the system. Given the costs of a meltdown, there is a possible role for government intervention. Unfortunately, liquidity and solvency problems interact and can cause each other, making it hard to determine the cause of a crisis. We propose a robust sequence of intervention.
The Stock Market's Reaction to Unemployment News: Why Bad News Is Usually Good for Stocks
Authors: BOYD JOHN H. , HU JIAN , JAGANNATHAN RAVI 
Published: March 2005

ABSTRACTWe find that on average, an announcement of rising unemployment is good news for stocks during economic expansions and bad news during economic contractions. Unemployment news bundles three types of primitive information relevant for valuing stocks: information about future interest rates, the equity risk premium, and corporate earnings and dividends. The nature of the information bundle, and hence the relative importance of the three effects, changes over time depending on the state of the economy. For stocks as a group, information about interest rates dominates during expansions and information about future corporate dividends dominates during contractions.