bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased O<sub>2</sub> Consumption and Positive Inotropy Caused by Cyclic GMP Reduction Are Not Altered after L-Type Calcium Channel Blockade
Authors: Leone Jr. Richard J. , Naim Karen L. , Scholz Peter M. , Weiss Harvey R. 
Published: April 2003

We tested the hypothesis that increased O<sub>2</sub> consumption and inotropy after reduction of myocardial cyclic guanosine monophosphate (cGMP) are mediated through L-type calcium channels. Anesthetized, open-chest New Zealand white rabbits were divided into four groups. Hearts were exposed to control vehicle (n = 8); LY83583 (LY, 10<sup>–3</sup> mol/l, guanylate cyclase inhibitor, n = 9); nifedipine (nif, 10<sup>–4</sup> mol/l, L-type calcium channel blocker, n = 8), or nif+LY (n = 6). Vehicle or compound was applied topically to the epicardium for 15 min. Subepicardial (EPI) blood flow increased (from 213 ± 22 to 323 ± 24 ml/min/100 g) in the presence of LY, as did subendocardial (ENDO) blood flow (from 238 ± 20 to 333 ± 38 ml/min/100 g). O<sub>2</sub> consumption increased in the presence of LY: 18.0 ± 1.0 (EPI) and 17.0±0.6 (ENDO) ml O<sub>2</sub>/min/100 g as compared with 9.5 ± 2.0 (EPI) and 10.6 ± 2.5 (ENDO) in the control group. The increase in O<sub>2</sub> consumption with LY was undiminished in the presence of nif (nif+LY group 21.0 ± 3.0 ml O<sub>2</sub>/min/100 g EPI and 22.1 ± 3.8 ENDO). Nif alone decreased left ventricular d<i>P</i>/dt<sub>max</sub> from (2,762 ± 197 to 2,413 ± 316 mm Hg/s) and maximal rate of change in wall thickness (d<i>W</i>/dt<sub>max</sub> from 13.5 ± 2.0 to 9.5 ± 0.8 mm/s), while percent change of wall thickness (from 21.3 ± 3.3 to 31.3 ± 7.2) and d<i>W</i>/dt<sub>max</sub> (from 13.3 ± 3.0 to 15.3 ± 2.3 mm/s) increased in the nif+LY group. Thus, the positive O<sub>2</sub> consumption and inotropic effects of decreasing cGMP were undiminished by nif. These results suggest that the cGMP reduction induced increases in O<sub>2</sub> consumption and that inotropy may not be mediated through L-type calcium channels.
Inhibition of Testicular Steroid Metabolism by Administration of 1-Aminobenzotriazole to Rats
Authors: Soltis Michael , Colby Howard D. 
Published: April 2003

Effects of 1-aminobenzotriazole (ABT) on testicular steroid metabolism were evaluated in rats. Administration of ABT to adult male rats caused dose-dependent decreases in testicular microsomal and mitochondrial cytochrome P450 concentrations. Significant losses of P450 occurred within 8 h of ABT treatment. Accompanying the declines in testicular P450 content were decreases in microsomal 17α-hydroxylase and mitochondrial cholesterol sidechain cleavage activities. Incubation of testicular microsomes or mitochondria in vitro with ABT plus an NADPH-generating system had no effect on P450 concentrations or on rates of steroid metabolism. By contrast, incubation of hepatic microsomes with ABT under the same conditions decreased P450 levels and xenobiotic-metabolizing activity. The results indicate that ABT in vivo causes inactivation of steroidogenic P450 isozymes in the testis, but the mechanism of inactivation differs from that on xenobiotic-metabolizing isozymes.
Differentiation of the Inhibitory Effects of Calcium Antagonists on Abnormal Behaviors Induced by Methamphetamine or Phencyclidine
Authors: Hori Yusuke , Takeda Hiroshi , Tsuji Minoru , Matsumiya Teruhiko 
Published: April 2003

The abnormal behaviors induced by methamphetamine (MAP: 1 mg/kg) or phencyclidine (PCP: 10 mg/kg) were measured using behavioral analysis following the microinjection of one of three calcium (Ca) antagonists (nifedipine: Nif, nicardipine: Nic and flunarizine: Flu) into the rat caudate putamen or amygdala. The intraperitoneal administration of MAP or PCP induced abnormal behaviors in a time-dependent manner; the maximum locomotor activity was measured 30–45 min after the administration of MAP or PCP. This hyperactivity was sustained for more than 2 h. Following microinjection of these Ca antagonists into the caudate putamen, each showed a different pattern of inhibition on MAP- or PCP-induced abnormal behaviors. Nic and Flu were effective at reducing these abnormal behaviors, in contrast, Nif was ineffective. In particular, the inhibitory effect of Nic was stronger than that of Flu. Microinjection of these Ca antagonists into the amygdala did not show any reductive effect on the hyperactivity induced by MAP or PCP. These results demonstrate that these Ca antagonists have different pharmacological properties and that both L- and T-type Ca<sup>2+</sup> channels modulate the dopamine release in the rat caudate putamen. These results further lead us to suggest the presence of a subtype of L-type Ca<sup>2+</sup> channels in the caudate putamen.
Esculentoside A Inhibits Tumor Necrosis Factor, Interleukin-1, and Interleukin-6 Production Induced by Lipopolysaccharide in Mice
Authors: Ju Dian Wen , Zheng Qin Yue , Cao Xuetao , Fang Jun , Wang Hong Bin 
Published: April 2003

Esculentoside A, a kind of saponin isolated from the root of the Chinese herb <i>Phytolaca esculenta</i>, is reported to possess potent anti-inflammatory effects in acute and chronic experimental models. In the present study, we investigated the effects of esculentoside A on the production of tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6) induced by lipopolysaccharide (LPS) in mice. In vitro experiments demonstrated that esculentoside A (0.1–10 µmol/l) significantly reduced the release of TNF from the peritoneal macrophages derived from mice pretreated with thioglycolate. IL-1 and IL-6 secretion was also obviously inhibited in a concentration-dependent manner by esculentoside A from 0.01 to 10 µmol/l. In vivo experiments demonstrated that detectable TNF was observed 0.25 h after injection, was maximal at 0.5 h, and returned to baseline at 4 h. Maximal production of IL-1 and IL-6 were observed to be 1 and 2 h, respectively, after injection of LPS. Pretreatment of mice with 5, 10, or 20 mg/kg esculentoside A once a day for 7 consecutive days dose-dependently decreased the TNF, IL-1 and IL-6 levels in the sera of mice following LPS challenge. TNF, IL-1, and IL-6 are important cytokines involved in the pathogenesis of inflammatory lesions. Inhibition of inflammatory cytokine production may contribute to the anti-inflammatory effects of esculentoside A.
Portal Hypotensive Effects of DL-028 and Prazosin on Portal Hypertensive Rats
Authors: Huang Yi-Tsau , Lin Li-Chih , Chern Ji-Wang , Lin Han-Chieh , Hong Chuang-Ye 
Published: April 2003

The portal hypotensive effects of prazosin and DL-028 (chem- ical name: 3-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]- 2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one(27b)), a synthetic α<sub>1</sub>-adrenoceptor antagonist, were assessed in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Two weeks after ligation, when the hyperdynamic state was stabilized the rats were anesthetized after an overnight fast and cannulated for measuring mean arterial pressure (MAP), portal venous pressure (PVP), cardiac index (CI) and heart rate (HR). Both DL-028 and prazosin (1, 3.3 and 10 µg/kg) induced dose-dependent decreases of PVP and MAP after intravenous infusion, with effects lasting for longer than 30 min. The maximum percentage reduction of PVP after DL-028 was 10, 10 and 15%, respectively, for the dosages given (1, 3.3 and 10 µg/kg), and 5, 12 and 25%, respectively, after prazosin. CI was not changed by either drug. HR was not changed by either drug except DL-028 at 10.0 µg/kg with a bradycardiac effect. Our results showed that both DL-028 and prazosin reduced PVP in portal hypertensive rats.
Contractile and Relaxant Effects of Tetrapentylammonium Ions in Rat Isolated Mesenteric Artery
Authors: Kwok K.H. , Chan N.W.K. , Lau C.W. , Huang Yu 
Published: April 2003

Both contractile and relaxant responses to tetrapentylammonium ions (TPA<sup>+</sup>) were studied in rat isolated mesenteric artery. TPA<sup>+</sup> (5–10 µmol/l) caused a sustained increase of muscle tension. The contractile effect of TPA<sup>+</sup> (10 µmol/l) was dependent upon the presence of extracellular Ca<sup>2+</sup> but independent of the presence of endothelium. TPA<sup>+</sup> (10–50 µmol/l) induced biphasic contraction, and the amplitude of peak and sustained tension decreased with increasing TPA<sup>+</sup> concentration. TPA<sup>+</sup> (100–300 µmol/l) only produced monophasic contraction. TPA<sup>+</sup> (50 µmol/l) abolished the transient contraction induced by caffeine (10 mmol/l) or phenylephrine (1 µmol/l) in the absence of extracellular Ca<sup>2+</sup>. Nifedipine and verapamil concentration-dependently reduced the TPA<sup>+</sup>-induced contraction with respective IC<sub>50</sub> values of 1.34 ± 0.24 and 9.46 ± 1.36 nmol/l, these values were similar to 1.35 ± 0.21 and 16.07 ± 1.71 nmol/l, respectively, for the inhibitory effects of nifedipine and verapamil on the high K<sup>+</sup> (60 mmol/l)-induced contraction. TPA<sup>+</sup> (>10 µmol/l) concentration-dependently reduced the phenylephrine (1 µmol/l)-, U46619 (30 nmol/l)-, endothelin I (10 nmol/l)- and high K<sup>+</sup> (60 mmol/l)-induced sustained tension with respective IC<sub>50</sub> values of 53.7 ± 9.5, 31.9 ± 5.3, 30.9 ± 3.4 and 20.9 ± 2.8 µmol/l. The present results indicate that TPA<sup>+</sup> at low concentrations could contract the arterial smooth muscle probably through promoting Ca<sup>2+</sup> influx. At higher concentrations (>20 µmol/l), TPA<sup>+</sup> relaxes arterial smooth muscle probably through inhibition of both nifedipine-sensitive Ca<sup>+</sup> channels and internal Ca<sup>2+</sup> release. TPA<sup>+</sup>, unlike other quaternary ammonium ions, could therefore act at multiple sites in arterial smooth muscle.
In vitro Biotransformation of a Novel Antimalarial Cysteine Protease Inhibitor in Human Liver Microsomes
Authors: Zhang Yuanchao , Guo Xisheng , Lin EmilT. , Benet LeslieZ. 
Published: April 2003

4-Dimethylamino-4′-(imidazol-1-yl)chalcone (RL3142) is a newly developed antimalarial cysteine protease inhibitor. Four metabolites (M1–M4) were found in human liver microsomes and their structures were identified by LC/MS/MS. Two primary metabolites, M2 (minor) and M4 (major), were determined to be the N-demethylated product (M2) and the product (M4) resulting from 1,2-hydrogenation of the α,β-unsaturated ketone moiety of the parent compound. A combined approach utilizing selective P<sub>450</sub> inhibitors, immunoinhibition with CYP3A and NADPH P<sub>450</sub> reductase antibodies, and cDNA expressed human CYP3A4 and NADPH P<sub>450</sub> reductase, was used for identification of enzymes responsible for the biotransformation. For formation of M2, both a rabbit CYP3A polyclonal antibody (110 µl/mg microsomal protein) and ketoconazole (2 µmol/l), a CYP3A inhibitor, showed about 50% inhibitory effects; other specific inhibitors of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP2E1 showed no significant effects. For formation of M4, neither CYP3A antibody nor the above mentioned CYP inhibitors exhibited inhibitory effects. Anti-rat NADPH P<sub>450</sub> reductase serum (50 µl/100 µg microsomal protein) exhibited 70 and 58% inhibitory effects on M2 and M4 formation, respectively. Incubation of RL3142 with cDNA expressed human NADPH P<sub>450</sub> reductase yielded formation of M4, but not M2. Carbon monoxide inhibited formation of M2 and M1 (the reduced product of M2), but had no effect on M4 and M3 (the reduced product of M4) formation. Collectively, NADPH P<sub>450</sub> reductase solely catalyzed reduction of RL3142 to M4, whereas CYP3A contributed in part to formation of M2.
Correlation between the in vivoEff icacy of GPIIb/IIIa Receptor Antagonists (m7E3, MK-383 and DMP-728) and ex vivo Platelet Inhibition
Authors: Huang Jinbao , Rebello Sam S. , Faul Jessica D. , Lucchesi Benedict R. 
Published: April 2003

In vivo antithrombotic efficacy of GPIIb/IIIa receptor antagonists (m7E3, MK-383 and DMP-728) was studied with respect to their ex vivo platelet inhibition in heparinized platelet-rich plasma (hPRP) and citrated platelet-rich plasma (cPRP) using a canine model of carotid artery thrombosis. For each drug group (n = 6), the right carotid artery was used as control vessel and resulting occlusive thrombus was kept in situ to examine the direct thrombolytic efficacy of the antagonists. Thirty minutes after occlusion of control vessel, a low or high dose of each antagonist was administered and the left carotid artery was used as test vessel. All control vessels occluded within 86–96 min in response to electrolytic injury. The incidence of occlusion with lower doses of m7E3, DMP-728, and MK-383 was 100, 33 and 100%, respectively; corresponding times to occlusion were 174, 220 and 118 min. Lower doses inhibited ADP- or AA-induced platelet aggregation in cPRP (>80%). Incidence of occlusion with high doses of m7E3, DMP-728 and MK-383 was 33, 0 and 0%, respectively; corresponding times to occlusion were 209, >240 and >240 min. Higher doses inhibited aggregation in cPRP (>80%), but only partially in hPRP (45–66%). Dose-dependent prolongation of bleeding time occurred with all antagonists. None of the antagonists lyzed preformed thrombi in control vessels. The results indicate that ex vivo platelet aggregation conducted in hPRP, as opposed to conventional cPRP, provides a better assessment of the in vivo efficacy of GPIIb/IIIa receptor antagonists.
Effects of Eprosartan on Glomerular Injury in Rats with Reduced Renal Mass
Authors: Gandhi Mehul , Meyer Timothy W. , Brooks David P. 
Published: April 2003

The effects of the selective angiotensin AT1 receptor antagonist, eprosartan, were evaluated in experimental renal disease. Five-sixth nephrectomy in male Munich-Wistar rats led to the development of hypertension, proteinuria and remnant glomerulosclerosis. Administration of the AT1 receptor antagonist, eprosartan, for 4 weeks resulted in inhibition of angiotensin II activity as confirmed by a reduced blood pressure response to exogenous angiotensin II challenge. Compared to vehicle treatment, eprosartan normalized blood pressure, reduced proteinuria and limited remnant glomerulosclerosis. These data suggest that eprosartan may provide a new tool in the treatment of progressive renal disease.
Insulin Reversal of Impaired Nitrergic Transmission in the Anococcygeus Muscle from Diabetic Rats
Authors: Way Kerrie J. , Reid Julianne J. 
Published: April 2003

The aim of this study was to investigate whether insulin could reverse the impairment in nitrergic neurotransmission in the anococcygeus muscle from streptozotocin-induced diabetic rats. Relaxations to nitrergic nerve stimulation and sodium nitroprusside were significantly reduced in precontracted muscles from 8- and 4-week diabetic rats compared to the corresponding control rats. Treatment of diabetic rats with Lente insulin (1–12 units/day s.c.) for the final 4 weeks of the 8-week diabetes duration reversed the reductions, but treatment of diabetic rats with insulin for the last week only did not. The impairment of relaxations was also not altered by in vitro exposure of muscles from 8-week diabetic rats to soluble insulin (0.02 units/ml, 2 h). The findings suggest that in vivo insulin treatment can reverse the existing diabetes-induced impairment of nitrergic transmission in rat anococcygeus muscle. However, short-term treatment with insulin, either in vivo or in vitro, does not reverse the impairment.
Meloxicam Inhibits Prostaglandin E<sub>2</sub> Generation via Cyclooxygenase 2 in the Inflammatory Site but Not That via Cyclooxygenase 1 in the Stomach
Authors: Ogino Keiko , Hatanaka Ko , Kawamura Michiko , Ohno Takashi , Harada Yoshiteru 
Published: April 2003

We studied the effects of meloxicam on prostanoid levels, both in the inflammatory site in rat carrageenin-induced pleurisy and in the rat stomach injected with 1 mol/l NaCl solution, to clarify the relationship between its low gastric toxicity and its relative cyclooxygenase (COX) 2 selectivity. NS-398 (3 mg/kg), a highly selective COX-2 inhibitor, and meloxicam (3 mg/kg) exhibited anti-inflammatory effects in the pleurisy model. Prostaglandin (PG) E<sub>2</sub> thromboxane (TX) B<sub>2</sub> and 6-keto-PGF<sub>1α</sub> were detectable in the inflammatory site. Anti-inflammatory doses of NS-398 and meloxicam each suppressed the intrapleural PGE<sub>2</sub> level at 5 h as potently as piroxicam (3 mg/kg) as aspirin (100 mg/kg), both of which are nonselective COX inhibitors. NS-398 was much less potent than the other three in suppressing the levels of TXB<sub>2</sub> and 6-keto-PGF<sub>1α</sub>. These results suggest that PGE<sub>2</sub> may be produced mainly via COX-2 in this model and that meloxicam may inhibit COX-2 in the inflammatory site. Piroxicam completely inhibited the increase in gastric PGE<sub>2</sub> induced by administering 1 mol/l NaCl solution into the rat stomach. Nimesulide (3 mg/kg), another selective COX-2 inhibitor, however, never affected this increase, suggesting that the gastric PGE<sub>2</sub> may be produced via COX-1. The anti-inflammatory dose of meloxicam caused statistically nonsignificant suppression of the PGE<sub>2</sub> level, by approximately 50%. These results suggest that the potent anti-inflammatory effect of meloxicam, accompanied with low gastric toxicity, may be related to its relative selectivity for COX-2 over COX-1.
Nasalization of Vowels in Nasal Environments in Babbling: Evidence for Frame Dominance
Authors: Matyear Christine L. , MacNeilage Peter F. , Davis Barbara L. 
Published: April 2003

Abstract
An emerging concept for the characterization of the form of babbling and early speech is ‘frame dominance’: most of the variance arises from a frame provided by open-close mandibular oscillation. In contrast, the tongue – the most versatile articulator in adults – plays only a minor role in intersegmental and even intersyllabic changes. The contribution of another articulator – the soft palate – to time-domain changes in babbling was evaluated in an acoustic analysis of 433 consonant-vowel-consonant sequences produced by 3 infants. Strong nasal effects on vowels in symmetrical consonantal environment were observed in the form of a lower frequency first formant region in low vowels and a lower frequency second formant region in front vowels. These results, the first of which also occurs in adults, were complemented by perceptual tendencies for transcribers to transcribe more mid vowels relative to low vowels and more central vowels relative to front vowels in nasal environments. Thus the soft palate is like the tongue in making only minor contributions to time-domain changes in babbling, and this is considered to be additional evidence for the frame dominance conception.
Consistency of Tone-Syllable Alignment across Different Syllable Structures and Speaking Rates
Authors: Xu Yi 
Published: April 2003

Abstract
Previous studies have reported that F₀ contours of lexical tones in Mandarin are closely aligned with the syllables that carry them and that this alignment is late-adjusted so that the most appropriate F₀ contour of a tone occurs mainly in the later portion of the host syllable. These studies, however, examined tone alignment only in syllables with a simple CV structure. The present study compared tone-syllable alignment patterns in syllables with a final nasal (the only final consonant allowed in Mandarin) to those without a final nasal at three speaking rates – normal, fast and slow. Experiment 1 found that regardless of internal syllable structure, the F₀ contours for all of the four Mandarin tones maintain a consistent alignment to the syllables that carry them. Experiment 2 found that whether or not the syllable has a final nasal and regardless of speaking rate, the F₀ peak associated with the R (rising) tone always occurs near the offset of the R-tone-carrying syllable, the onset of the F₀ rise always occurs near the center of the syllable and the slope of the rise does not vary systematically with either syllable structure or speaking rate. These findings are interpreted as indicating that the syllable is the proper domain for tone implementation and that tone contours such as rising and falling are probably implemented as integral dynamic targets rather than as sequences of static targets.
Thai Final Stops: Cross-Language Perception
Authors: Abramson Arthur S. , Tingsabadh Kalaya 
Published: April 2003

Abstract
As part of a project seeking a better understanding of the links between speech production and perception, we have conducted experiments on the perception of Thai word-final stop consonants by native speakers of Thai and native speakers of American English. The final stops of Thai are never released audibly. In English, however, final stops occur with and without audible releases. Previous work has shown that released stops are likely to be more intelligible than unreleased ones. That is, identification is better when information as to place of articulation in the formant transitions of the closing articulatory gesture is supplemented by acoustic information in a release burst. Both languages have labial, alveolar, and velar places of articulation, but Thai also has glottal closure. Two native speakers of Thai recorded sets of monosyllabic words minimally distinguished by the four final stops . Randomized lists of the isolated words were presented to 19 native speakers of English who responded with the labels ‘p’, ‘t’, ‘k’, and ‘other’. They were also presented to 30 native speakers of Thai for identification in Thai script as words. The highly significant differences between the two groups imply the possibility that the closing gestures of the Thai stops include a component that compensates somewhat for the absence of release, a component to which the English speakers are perhaps less well attuned. Such an interference will be tested in future work by tracking of the gestures in both languages with the Haskins Laboratories magnetometer.
Singing Birds, Playing Cats, and Babbling Babies: Why Do They Do It?
Authors: Sjölander Sverre 
Published: April 2003

Abstract
Rarely, animals do what they do because they are aware of the function of the behaviour or its outcome. Instead, they will very often perform behaviour out of context, spontaneously, as play. The impression (strengthened by introspection in the human species) is that they do it because they get some kind of internal reward. Nevertheless, such seemingly meaningless behaviour may have an ultimate function to adjust behavioural programs to the body, to practice, to perfect the execution of the behaviour. If the proximate reason for doing what the animal does may be to attain a pleasurable state, the ultimate, evolutionary reason may still be that increased practice will give some gain in fitness. If one presupposes internal rewarding and punishing systems as intervening factors, it becomes much simpler to explain why birds sing, kittens play or babies babble without any outer reward and out of any functional context, more than needed from a strictly functional view, spontaneously and just for the fun of it.
Effects of Proteins, Blood Cells and Glucose on the Viscosity of Cerebrospinal Fluid
Authors: Bloomfield I.G. , Johnston I.H. , Bilston L.E. 
Published: April 2003

It has long been assumed that cerebrospinal fluid (CSF) is a newtonian fluid with viscosity similar to water, yet high protein content, has been postulated to increase the viscosity of CSF in vivo. Such an increase in viscosity may have serious implications for the effectiveness of surgical shunts implanted to re-establish the CSF flow in cases of abnormal CSF circulation. In this study, glucose content, total protein content and blood cell count in the CSF of 23 patients undergoing brain surgery were measured. Viscosity measurements were performed on duplicate CSF samples over a range of shear strain rates of 25–1,460 s<sup>–1</sup>. The results indicated that high protein or high cell concentration in CSF does not significantly affect the viscosity of the cerebral fluid at those shear rates. CSF is clearly newtonian, and its viscosity at 37°C is in the range of 0.7–1 mPa·s.