bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiostatic cortexone‐heparin combination treatment suppresses chronic granulomatous inflammation in mice
Authors: Dunn Colin J. , Galinet Louise A. 
Published: January 2005

AbstractCombined steroid‐heparin therapy has been shown to inhibit angiogenesis and tumor growth. We therefore decided to test the antiinflammatory activity of this combination therapy using “cotton pellet” and “delayed‐type hypersensitivity” granuloma reactions, which display a high degree of angiogenesis. Subcutaneous injection of cortexone (deoxycorticosterone) caused significant suppression of both granulomatous reactions only when administered to mice receiving heparin ad libitum in the drinking water. Significant reduction in inflammatory leukocyte infiltration and angiogenesis was also observed histologically compared with controls. Coretexone or heparin alone failed to alter the granulomatous responses. Hematomas were observed only in the cortexone‐heparin combination therapy group at the cortexone subcutaneous injection site suggesting a possible effect on endothelial cell integrity; blood coagulation times remained unaltered, and no evidence of hemorrhage was observed at autopsy. Modest loss in thymic weight occurred only in mice receiving cortexone (100 mg/kg/day s.c.), regardless of concomittant heparin treatment. We conclude that combination cortexone‐heparin treatment causes significant inhibition of chronic granulomatous inflammation, which is independent of glucocorticoid or coagulation mechanisms. Further investigation is required to determine whether this effect is accomplished via inhibition of macrophage function, endothelial cell proliferation, or interference with tissue matrix metabolism.
Cyclosporine uptake by cultured human proximal tubule cells
Authors: Kahng Myong Won , Lee Jung Young , Trifillis Anna L. 
Published: January 2005

AbstractCharacteristics of cyclosporine A (CsA) uptake in cultured normal human proximal tubule cells (PTC) have been studied. The uptake was very rapid, concentration dependent, and reached a steady state level within 10 min. Kinetic analysis yielded an apparent Km of 5.0 μM and Vmax of 66.7 pmoles/min μg DNA. Verapamil, a calcium channel blocker, at 0.1, 0.5, and 1.0 mM had no inhibitory effect on CsA uptake. Subcellular distribution of CsA following 1, 2, 5, and 10 min incubation of PTC suspension was determined by digitonin differential solubilization. The cytosol fraction contained 26% and the nuclear fraction contained 74% of CsA at all time periods studied. These studies demonstrate that in normal human renal PTC, uptake of CsA is rapid and saturable. Most of the CsA, once taken up by the human PTC, is concentrated in the nucleus.
Co‐mitogenic assay for assessing the effects of aflatoxin B1 on interleukin‐1 production in bovine macrophages
Authors: Walsh Catherine J. , Bodine Ashby B. , Scott Thomas R. 
Published: January 2005

AbstractPrevious research has shown that aflatoxin B1 (AFB1) markedly decreases the uptake of tritiated thymidine in bovine peripheral lymphocytes. Currently, the immunosuppressive activities of aflatoxin B1 are being investigated further using bovine macrophages as a model cell type. Polystyrene‐adhered macrophages demonstrated a 50% reduction in up‐take of tritiated thymidine at 10 μg/mL aflatoxin B1. The distribution of 3H‐AFB1 in bovine macrophages was investigated to study mechanisms by which AFB1 may be exerting immunosuppressive effects. Only 12.96% of the incorporated 3H‐AFB1 was taken into nuclear DNA, whereas 80.13% remained in the cytosolic fraction. A co‐mitogenic assay was developed to ascertain the correlation between reduced tritiated thymidine uptake, binding of 3H‐AFB1 to nuclear DNA, and interleukin‐1 (IL‐1) production and/or activity. Conditioned media containing interleukin‐1 activity was prepared by culturing macrophages for 24 hr with 2.5 μg/mL lipopolysaccharide, 45 ng/mL phorbol myristate acetate, with or without 10 μg/mL aflatoxin B1. The conditioned media was used in a co‐mitogenic assay with calf thymocytes as target cells. In this assay, the response of calf thymocytes to conditioned media from AFB1‐treated cells did not differ from the response to control conditioned media. In addition, AFB1 added to thymocyte cultures co‐stimulated with conditioned media and concanavalin A (ConA) greatly diminished the thymocyte response to co‐stimulation. The data support the conclusions that the immunosuppressive effects of AFB1 on the bovine macrophage and T lymphocyte may not be directly related via impaired IL‐1 production. The blinding of AFB1 to macrophage DNA was not sufficient to produce any detectable effect on interleukin‐1 production by bovine macrophages.
Effects of a low‐doses treatment with cuprum on neostigmine digestive action in female mice
Authors: Santini R. , Tessier M. , Belon P. 
Published: January 2005

AbstractA low‐doses treatment with cuprum 4CH, 24 and 5 hr before neostigmine (50 μg/kg/IP) administration, has been done in the female mouse. This treatment significanlty reduces (Kruskal‐Wallis—P < 0.02) the facilitating action of neostigmine on intestinal transit. Cuprum 4CH treatment administered alone has no significant effect on transit.
Functional link between myocardial α1‐ and β1‐adrenoceptors in neonatal rabbits
Authors: Varma Daya R. 
Published: January 2005

AbstractOntogeny of inotropic responses of the left atria and chronotropic responses of the right atria of rabbits was studied in vitro. The maximal inotropic effect (efficacy) of isoproterenol on atria from neonatal (1.5 weeks old) rabbits was significantly less than that of norepinephrine and epinephrine. The inotropic efficacy of isoproterenol increased with age and reached adult levels at 6 weeks. There was no difference in the potency and efficacy of inotropic effects of epinephrine and norepinephrine on neonatal and adult (∼40 weeks old) rabbit atria. At threshold concentrations, phenylephrine synergistically potentiated the inotropic effects of isoproterenol on atria from neonatal but not on atria from adult rabbits. The potentiation of the inotropic effects of isoproterenol by phenylephrine on neonatal rabbit atria was abolished by prazosin. There was no difference in the chronotropic effects of isoproterenol on atria from neonatal and adult rabbits. It is speculated that α1‐ and β1‐myocardial adrenoceptors are functionally linked in early life and a full expression of inotropic responses requires a concomitant activation of both receptor types.
Comparative effects of linogliride fumarate and tolbutamide sodium on insulin secretion and glucose utilization in rat pancreatic islets
Authors: Tuman Robert W. , Morris David M. , Bryan Debra J. , Wallace Nathanial H. , Voina Sandra J. , Bowden Charles R. , Tutwiler Gene F. 
Published: January 2005

AbstractThe effects of linogliride fumarate (0.1 mmol/liter) and tolbutamide sodium (0.5 mmol/liter) on insulin secretion and glucose utilzation were directly compared in isolated perifused rat islets. Both compounds potentiated glucose‐primed (5.5 mmol/liter) insulin release. The insulin secretory response at the concentration chosen was qualitatively different for the two agents. In the presence of glucose, the insulin secretory effect of tolbutamide was biphasic, whereas linoglirde predominantly increased second‐phase insulin secretion. In the absence of exogenous glucos, tolbutamide stimulated first‐phase insulin release wherease linogliride was ineffective without glucose in the perifusion medium. Neither linogliride (0.1 mmol/liter) nor tolbutamide (0.5 mmol/liter) stimulated islet cell glucose usage as measured by conversion of [5−3H]‐glucose to 3H2O. The insulin secretagogue effect of linogliride was completely abolished when islet cell glucose usage was partially blocked (22% reduction) by mannoheptulose (MH) (10 mmol/liter). When glucose usage was significantly inhibited (55%) by 2‐deoxyglucose (2DG) (10 mmol/liter), linogliride‐stimulated insulin secretion was not significantly reduced. In contrast, tolbutamide‐stimulated first‐phase insulin release was not inhibited when glucose usage was reduced by either MH or 2‐DG, wherease secondphase insulin release was significantly inhibited. In summary, linogliride potentiates insulin secretion in isolated islets by a glucose‐dependent process, but with a kinetic profile and response to metabolic inhibitors different from that of tolbutamide.
L‐683,877: Pharmacological profile of a novel 5‐HT3 receptor antagonist
Authors: Tattersall David , Newberry Nigel , Beer Margaret S. , Rigby Mike , Gilbert Michael , Maguire Janet J. , Mudunkotuwa Nikki , Duchnowski Mark , McKnight Alexander T. , Swain Christopher J. , Kneen Clare , Dourish Colin T. 
Published: January 2005

AbstractThe 5‐HT3 receptor antagonist properties of the novel compound L‐683,877 (−) (2′‐(1‐methyl‐1H‐indol‐3‐yl)‐)spiro(1‐azabicyclo[2.2.2]octane‐3,5′(4′H)‐oxazole) have been characterised in vitro and in vivo. In radioligand binding studies, L‐683,877 displaced [3H]quaternized ICS 205–930 binding to membranes of rat cortex with a pKi of 8.71. L‐683,877 was essentially inactive (pKi<5) at 5‐HT1A, 5‐HT1B, 5‐HT1C, 5‐HT1D, 5‐HT2, and dopamine D1 and D2 binding sites. In the rat isolated vagus nerve and superior cervical ganglion (SCG) preparations, L‐683,877 antagonized 5‐HT3 agonist‐induced depolarizations with apparent pKB values of 9.30 and 8.25, respectively. Similarly L‐683,877 antagonized the positive chronotropic effects of 5‐HT in the isolated rabbit heart preparation (apparent pKB 10.10). In the anaesthetized rat, L‐683,877 (10–100 μg kg−1 i.v.) antagonized the Bezold Jarisch reflex evoked by 5‐HT; at a dose of 10 μg kg−1 i.v. L‐683,877 caused a twofold shift in the dose response curve. The retching and vomiting response induced in the ferret by cisplatin (10 mg kg−1 i.v.), was markedly attenuated by L‐683,877 (0.1 mg kg−1 i.v. and p.o.) and completely prevented by higher doses (10 mg kg−1 i.v. and p.o.). These data indicate that L‐683,877 is a potent and selective 5‐HT3 receptor antagonist.
Evaluation of the discriminative stimulus effects of venlafaxine, a potential antidepressant, in rhesus monkeys
Authors: Nader Michael A. , Woolverton William L. 
Published: January 2005

AbstractThe discriminative stimulus effects of the novel antidepressant venlafaxine were examined in rhesus monkeys. Separate groups of monkeys discriminated either 0.56 or 1.0 mg/kg (i.g.) d‐amphetamine (N = 3) or 10 mg/kg (i.g.) pentobarbital (N = 4) from saline, in a discrete‐trials shock avoidance/escape paradigm. In d‐amphetamine‐trained monkeys, 10–17 mg/kg venlafaxine occasioned only saline‐appropriate responding and had minimal effect on response latency in alll monkeys. The highest dose of venlafaxine tested (30 mg/kg) occasioned at least 95% d‐amphetamine‐lever responding in two of three monkeys. Following this dose, the average latency to respond after the onset of a trial increased substantially in both monkeys; in one monkey avoidance responding was disrupted and shocks were occasionally received. In the third monkey, 30 mg/kg venlafaxine occasioned only saline‐lever responding and had no effect on response latency. In pentobarbital‐trained monkeys, venlafaxine (3.0–30 mg/kg) occasioned primarily saline‐lever responding and these doses had minimal effects on response latency. In general, venlafaxine was more potent in d‐amphetamine‐trained monkeys than in pentobarbital‐trained monkeys in its effects on response latency. Drug discrimination procedures in animals have been shown to differentiate compunds in a manner that is consistent with their subjective effects. Thus, result from the present experiment suggest that venlafaxine may produce subjective effects similar to d‐amphetamine in some individuals, but only at high doses.
Natriuretic and diuretic effects of cicletanine in conscious, hydrated, normotensive rats
Authors: Buchholz R. Allan , Brousseau Armand , Silver Paul J. 
Published: January 2005

AbstractThe natriuretic and diuretic actions of cicletanine, a novel agent with vasorelaxant and antihypertensive properties, were examined in conscious, hydrated, normotensive rats. Cicletanine, the (+)‐ and (−)‐enantiomers of cicletanine, hydrochlorothiazide (HCTZ), or vehicle(s) were administered orally or intravenously (1, 3, 10, 30 mg base/kg) to water‐loaded (27 ml/kg) rats and 3 hr urine volume, Na+ and K+ were measured. Racemic cicletanine (3 mg/Kg, p.o.) caused a significant increase in urinary Na+(+174%) and K+ (+46%) excretion, unaccompanied by diuresis. Diuresis was detected only with larger oral doses of racemic cicletanine (10–30 mg/kg). Oral administration of a 1‐mg/kg dose of (+)‐cicletanine caused significant natriuresis that was not detected with either racemic or (−)‐cicletanine. The (+)‐enantiomer (3–30 mg/kg) produced natriuresis and diuresis quantitatively similar to that of racemic cicletanine. By contrast, (−)‐cicletanine induced only slight natriuresis, kaliuresis, and diuresis upon administration of the largest dose (30 mg/kg, p.o.). Intravenous administration of the racemate and enantiomers of cicletanine caused natriuretic/diuretic activity that was very similar to that seen with oral administration. The natriuresis caused by a 3‐mg/kg dose of racemic cicletanine was unaffected by indomethacin. However, indomethacin attenuated the natriuresis and eliminated the diuresis produced by the 10‐ and 30‐mg/kg doses of cicletanine. Indomethacin had no effect on the kaliuretic actions of cicletanine. Indomethacin blunted the natriuresis and eliminated the diuresis caused by all doses of HCTZ. In conclusion, the natriuretic, kaliuretic, and diuretic effects of racemic cicletanine in the conscious, hydrated, normotensive rat appear to be mediated primarily by the ( + )‐enantiomer. A dose‐dependent separation exists between the natriuretic and diuretic actions of cicletanine, with only natriuresis noted at smaller doses. The natriuresis caused by racemic cicletanine has both indomethacin‐resistant and indomethacin‐sensitive components, while cicletanine‐induced diuresis appears to be mediated exclusively by prostaglandins.
Novel low‐molecular‐weight superoxide dismutase mimic deferoxamine‐manganese improves survival following hemorrhagic and endotoxic shock
Authors: De Garavilla Lawrence , Chermak Timothy , Valentine Heather L. , Hanson Robert C. 
Published: January 2005

AbstractThe purpose of this study was to demonstrate the in vivo activity of the novel low‐molecular‐weight superoxide dismutase (SOD)‐mimic deferoxamine‐manganese (Def‐Mn) in models of circulatory shock. Two forms of Def‐Mn were examined: the pink‐complex (NPC 14550) and the green complex (NPC 15823). Hemorrhagic shock was induced in rats (40 mmHg, 60 min) followed by autotransfusion of shed blood, and endotoxic shock (LPS, 200 μg/10g BW) was induced in mice. Significant lethality (ca. 20% survival rate at 24 hr) was observed in each model. Following hemorrhagic shock, NPC 14550 (10 mg/kg) increased the 24‐hr survival rate to 48% (P=0.03), while NPC 15823 (10 mg/kg) did not significantly alter survival rate (30%, P > 0.05). Following endotoxin challenge, both NPC 14550 and NPC 15823 significantly improved the 24‐hr survival rate to 68% (P≤0.001) and 55% (P=0.002), respectively. Bovine erythrocyte SOD and polyethylene glycol‐SOD (Peg‐SOD) also afforded significant protection in these models and, as anticipated, SOD afforded transient protection, while Peg‐SOD provided significant protection for 24 hr and longer. Deferoxamine mesylate provided only transient protection. It is concluded that the SOD‐mimic Def‐Mn has beneficial effects following circulatory shock and, furthermore, these data provide additional evidence that the superoxide radical does play a role in these disorders.
Overview of the CNS pharmacology of BW 1370U87: A chemically novel, reversible, selective MAO‐A inhibitor with potential to be a new antidepressant drug
Authors: Cooper B. R. , White H. L. , Beek O. , Norton R. M. , Rigdon G. C. , Howard J. L. , Kraemer G. W. , Ferris R. M. 
Published: January 2005

AbstractBW 1370U87 is a potent, reversible, selective inhibitor of rat and human brain MAO‐A with a competitive mechanism of action. The ED50 of BW 1370U87 for inhibition of MAO‐A in rat brain is 8 mg/kg after oral administration, and the duration of action exceeds 7 hr. The ED80 dose for inhibition of MAO‐A (20 mg/kg) elevates NE, DA, and 5‐HT levels in brains of rats without significantly potentiating the blood pressure effects of a 15 mg/kg oral dose of tyramine. This dose of tyramine, extrapolated to man, exceeds the amount that could be consumed at one time from dietary sources. No inhibition of MAO‐B has been observed with BW 1370U87 either in vitro or ex vivo. BW 1370U87 was effective in the 5‐hydroxytryptophan potentiation test over the dose range that produced MAO‐A inhibition in brain in both rats and mice, and it reduced swim stress induced immobility in the Porsolt test. The compound has positive effects on abnormal social behavior produced by early social deprivation in the rhesus monkey. BW 1370U87 had no adverse cardiovascular effects in dogs or rats. It also had no significant pharmacological effects on various isolated tissue preparations and did not cause changes in the neuronal transport or the receptor systems which mediate the antidepressant effects or side effects of the tricyclic antidepressants. An acute oral dose 100 times that which produced an 80% inhibition of brain MAO‐A exhibited no signs of toxicity. BW 137OU87 appears to be a safe reversible MAO‐A inhibitor with potential for treating depression, anxiety conditions, panic, phobias, obsessive compulsive behaviors, and borderline personality disorders.
BW 1370U87, a new monoamine oxidase‐A inhibitor: Effects on biogenic amine neurotransmitter and metabolite levels in rat brain
Authors: Jones‐Humble Stacey A. , Norton Ron M. , White Helen L. , Cooper Barrett R. 
Published: January 2005

AbstractMonoamine oxidase (MAO) inhibitors increase brain concentrations of biogenic amines and decrease concentrations of the acidic metabolites of biogenic amines. It has been suggested that the magnitude of these effects is an indicator of MAO inhibition. Oral doses of BW 1370U87, moclobemide, and brofaromine were given to rats at doses previously shown to induce brain MAO‐A inhibition by at least 80%. The effects on brain biogenic amines and their metabolites were quantified 2 and 4 hr after oral dosing using HPLC with electrochemical detection. Moclobemide and BW 1370U87 induced larger increases in 5HT, NE, and DA and larger decreases in DOPAC, 5HIAA, and HVA than did brofaromine at the doses tested. At 8 hr post‐dose the effects of BW 1370U87 on 5HT, NE, DOPAC, and HVA were still significant (P≤0.05), and the time course was similar to that seen following moclobemide and brofaromine treatment. Only BW 1370U87 increased brain concentrations of biogenic amines at a dose that does not significantly potentiate pressor effects of orally administered tyramine.
Potentiation of the behavioral effects of 5‐hydroxytryptophan by BW 1370U87, a selective monoamine oxidase‐A inhibitor
Authors: Burchall Christopher J. , Soroko Francis E. , Rigdon Greg C. 
Published: January 2005

AbstractBW 1370U87, a novel, selective, reversible monoamine oxidase‐A inhibitor, was tested in the 5‐HTP (5‐hydroxytryptophan) potentiation test in mice and rats to establish its activity following systemic administration, to determine its duration of action and to determine if its effects were reversible in vivo. The behavioral effects of a threshold dose of 5‐HTP were potentiated by BW 1370U87 in mice with ED50s of 3.4 mg/kg i.p. and 18.4 mg/kg p.o. 5‐HTP potentiation occurred in rats with an ED50 of 10.4 mg/kg p.o. BW 1370U87 (20 mg/kg) was active 9 hr, but not 16 hr following oral administration, consistent with reversible enzyme inhibition.
Metabolism of BW 1370U87 in rat, dog, and man
Authors: Harrelson Jane Croft , Johnson Thomas E. , White Helen L. , Welch Richard M. 
Published: January 2005

AbstractBW 1370U87 is a potent, selective inhibitor of rat and human brain MAO‐A. The plasma concentrations of BW 1370U87 and its metabolites were determined in rat, dog, and man. After an oral dose, BW 1370U87 undergoes extensive first‐pass metabolism in all species studied. The 1‐(1,2, dihydroxyethyl) metabolite, BW 1003U88, was a major metabolite in rat, dog, and human plasma. The 1‐(1‐hydroxyethyl) metabolite, BW 183U88, was a major metabolite in dog plasma, whereas it was present in much lower concentrations in the rat and man. Both BW 1003U88 and BW 183U88 are active MAO‐A inhibitors although not as active as the parent compound. The inactive 1‐(2‐acetic acid) metabolite, BW 1552U88, was a major metabolite in rat plasma but a minor metabolite in the dog. Plasma concentration versus time profiles in both rat and man suggest that the metabolites undergo enterohepatic recycling. Although plasma concentrations of BW 1370U87 were relatively low compared to the metabolites, the concentrations detected in rat and man after a 50 mg/kg or 400 mg oral dose, respectively, exceeded the IC50 value measured in rat and human brain. Furthermore, the time course of MAO‐A inhibition appears to follow the plasma concentration versus time profile of BW 1370U87 in the rat. Preliminary experiments in rats indicate that BW 1370U87 and its metabolites distribute into brain and inhibit MAO‐A.
Effects of L‐alpha‐glycerylphosphorylcholine on the EEG power spectrum in the rat
Authors: Lacomba Corrado , Cagiano Raffaele , Maci Oronzo , Valerio Jaqueline , Cuomo Vincenzo 
Published: January 2005

AbstractThe effects of L‐alpha‐glycerylphosphorylcholine (alpha‐GPC), a putative acetylcholine precursor, on the EEG power spetrum in rats were investigated. The results show that the oral administration of alpha‐GPC (100–300–600 mg/kg) induced a significant decrease in absolute spectral energy in the delta frequency band. A significant increase in absolute spectral energy in the beta frequency band was elicited by alpha‐GPC at dose levels of 100 and 300 mg/kg, while the administration of a higher dose (600 mg/kg) of this compound resulted in the loss of response (bell‐shaped dose‐response curve). No significant changes in the EEG power spectrum were found in rats treated with phosphatidylcholine (PC).The present data, suggesting that the electrocorticographic (ECoG) activation elicited by alpha‐GPC may be correlated with its stimulatory effect on brain acetylcholine release, further extend the pharmacological profile of this new cognition enhancer. © 1992 Wiley‐Liss, Inc.