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Experiment II (experiment + ii)

Distribution by Scientific Domains

Medical Sciences	52%
Chemistry	21%
Life Sciences	15%

Selected Abstracts

Changes in the scrotal temperature of subjects in a sedentary posture over a heated floor

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 4 2006
Gook-Sup Song
Summary As Koreans habitually sit on the heated floor in their residential buildings, the male testis is directly exposed, and is therefore affected by the floor surface temperature. The purpose of this study was to investigate the changes in the scrotal temperature of the subjects in a sedentary posture over the heated floor. A rigid screening test was performed to select healthy subjects. Finally, six college students volunteered to participate in the experiments. Two experiments were performed in a controlled environmental chamber. Experiment I was designed for a low metabolism state, with the subjects reading a book in a sedentary posture for 50 min. The floor surface temperature (tf) was controlled by varying the temperature of water (tw) flowing into the floor coil from 15 to 50 °C, at 5 °C intervals. Experiment I revealed that the final scrotal surface temperature was 32.27, 32.62, 33.51, 33.34, 34.14, 34.28, 34.34 and 35.04 °C at the tw 15 °C (tf 17.0 °C), 20 °C (tf 20.8 °C), 25 °C (tf 24.1 °C), 30 °C (tf 27.8 °C), 35 °C (tf 31.7 °C), 40 °C (tf 35.9 °C), 45 °C (tf 38.6 °C) and 50 °C (tf 42.2 °C), respectively. At tf 17.0 and 20.8 °C, the scrotal temperature exhibited a declining pattern and a low temperature for spermatogenesis. At tf 24.1, 27.8 and 31.7 °C, however, the thermal regulatory system of the scrotum and testis was activated appropriately. On the contrary, scrotal temperature ascended at tf 35.9, 38.6 and 42.2 °C. Of the six subjects, two subjects demonstrated scrotal temperatures above 35 °C at tf 38.6 °C and four subjects exhibited scrotal temperatures above 35 °C at tf 42.2 °C. Experiment II was designed for a high metabolism state, with the subjects playing a card game in a sedentary posture for 180 min. The tf was controlled by varying the tw from 30 to 40 °C, at 5 °C intervals. Experiment II revealed that the final scrotal temperature was 33.43, 34.78 and 35.61 °C, and the difference between the initial and final scrotal temperatures was +0.34, +1.06 and +2.24 °C, at tw 30 °C (tf 27.8 °C), 35 °C (tf 31.7 °C) and tw 40 °C (tf 35.9 °C), respectively. The scrotal temperature was affected by the floor surface temperature and by the rate of metabolism of the subject in a sedentary posture. As derived from regression analysis, the recommended surface temperature of a heated floor is within 23,33 °C under the assumption that scrotal and consecutively testicular temperature above 35 °C impairs spermatogenesis. [source]

Prenatal testosterone treatment potentiates the aggression-inhibiting effect of the neurosteroid dehydroepiandrosterone in female mice

AGGRESSIVE BEHAVIOR, Issue 2 2001
Fabrice Perché
Abstract The neurosteroid dehydroepiandrosterone (DHEA) is a powerful inhibitor of aggression in murine models when given for 15 days and potentially may be useful in the management of inappropriate human aggression. Although the biosynthesis and metabolism of DHEA have been described, little is known about the potential effect of the steroidal environment during sexual differentiation on the subsequent response to DHEA. Whether prenatal androgen exposure influences the subsequent response to DHEA was assessed by comparing the effect of DHEA (80 ,g/d) on aggression in female offspring where dams were treated with 1, 10, or 100 ,g of testosterone (T) on days 15 to 18 of gestation (Experiment I) or that developed in different uterine positions (Experiment II). The results showed that DHEA decreased attack behavior in general and that the 100-,g prenatal T treatments enhanced the antiaggressive effect of this neurosteroid. Neither the lower doses of exogenously administered T nor the uterine position led to an enhanced response to DHEA. In addition, whether DHEA produced changes in social and nonsocial activities was examined. In the 100-,g T females, DHEA increased the duration of the former and decreased the frequency and duration of the latter, indicating that it was not a general decrement in behavioral expression that mediated the enhanced response to the antiaggressive effect of DHEA. In the second experiment, DHEA treatment led to increased frequencies of social nonaggressive and nonsocial activities. However, the uterine positions × treatment interactions were not significant, demonstrating that contiguity to male fetuses did not differentially affect the response to DHEA. Aggr. Behav. 27:130,138, 2001. © 2001 Wiley-Liss, Inc. [source]

Combined Scopolamine and Ethanol Treatment Results in a Locomotor Stimulant Response Suggestive of Synergism That is Not Blocked by Dopamine Receptor Antagonists

ALCOHOLISM, Issue 3 2009
Angela C. Scibelli
Background:, Muscarinic acetylcholine receptors (mAChRs) are well positioned to mediate ethanol's stimulant effects. To investigate this possibility, we examined the effects of scopolamine, a receptor subtype nonselective mAChR antagonist, on ethanol-induced stimulation in genotypes highly sensitive to this effect of ethanol. We also investigated whether the dopamine D1-like receptor antagonist, SCH-23390 or the dopamine D2-like receptor antagonist, haloperidol, could block the extreme stimulant response found following co-administration of scopolamine and ethanol. Methods:, Scopolamine (0, 0.0625, 0.125, 0.25, or 0.5 mg/kg) was given 10 minutes prior to saline or ethanol (0.75 to 2 g/kg) to female FAST (Experiment I) or DBA/2J (Experiment II) mice that were then tested for locomotion for 30 minutes. In Experiments III and IV, respectively, SCH-23390 (0, 0.015, or 0.03 mg/kg) was given 10 minutes prior, and haloperidol (0, 0.08, or 0.16 mg/kg) was given 2 minutes prior, to scopolamine (0 or 0.5 mg/kg), followed 10 minutes later by saline or ethanol (1.5 g/kg) and female DBA/2J mice were tested for locomotion for 30 minutes. Results:, FAST and DBA/2J mice displayed a robust enhancement of the locomotor effects of ethanol following pretreatment with scopolamine that was suggestive of synergism. SCH-23390 had no effect on the response to the scopolamine + ethanol drug combination, nor did it attenuate ethanol- or scopolamine-induced locomotor activity. Haloperidol, while attenuating the effects of ethanol, was not able to block the effects of scopolamine or the robust response to the scopolamine-ethanol drug combination. Conclusions:, These results suggest that while muscarinic receptor antagonism robustly enhances acute locomotor stimulation to ethanol, dopamine receptors are not involved in the super-additive interaction of scopolamine and ethanol treatment. They also suggest that in addition to cautions regarding the use of alcohol when scopolamine is clinically prescribed due to enhanced sedative effects, enhanced stimulation may also be a concern. [source]

The effects of vasoactive agents, platelet agonists and anticoagulation on thrombelastography

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2007
J. Kawasaki
Background:, Platelet activation is a critical step in primary hemostasis and clot formation. We tested a hypothesis that platelet stimulating effects of vasoactive agents or platelet agonists could be shown using thrombelastography (TEG®) as faster onset or increased clot strength. We further examined if TEG® could be modified to evaluate activated platelets as a reversal of anticoagulation in the presence of partial thrombin inhibition. Methods:, Blood samples were obtained from 126 non-cardiac surgical patients. Effects of vasoactive agents on TEG® and aggregometry were examined using epinephrine, norepinephrine, vasopressin, desmopressin acetate, milrinone and olprinone (Experiment I). Platelet agonists (epinephrine, ADP and collagen) were separately tested on TEG® (Experiment II). Effects of platelet agonists (ADP and collagen) on TEG® under anticoagulation in the absence or presence of abciximab were studied (Experiment III). We also tested antiplatelet effects of milrinone and olprinone in the presence of anticoagulants on TEG® (Experiment IV). Results:, Neither vasoactive agents nor platelet agonists affected TEG® or aggregometry results except for milrinone and olprinone on aggregometry (Experiment I, II). Platelet agonists facilitated clotting in the presence of anticoagulants (Experiment III). Abciximab-treated platelets still exhibited procoagulant effects in the presence of heparin, while not in the presence of argatroban (Experiment III). Platelet inhibition on the modified TEG® was more extensive with milrinone than olprinone, and it was dose dependent (Experiment IV). Conclusion:, Modified TEG® using heparin or argatroban might delineate the procoagulant effects of platelets by adding platelet specific agonist. [source]

Enhanced plasma and target tissue availabilities of albendazole and albendazole sulphoxide in fasted calves: evaluation of different fasting intervals

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2000
S. SÁNCHEZ
The influence of different pre- and post-treatment fasting periods on the plasma availability and disposition kinetics of albendazole (ABZ) and its sulphoxide metabolite (ABZSO) in cattle was investigated. The effect of fasting on the distribution of ABZ and ABZSO to different target tissues/fluids was also characterised. In Experiment I, 35 parasite-free Holstein calves were divided into seven groups according to the following feeding conditions and treated intraruminally with ABZ (10 mg/kg): control group (fed ad libitum), 24 h fasting either prior to (24 h pre-) or post (24 h post-) treatment, 24 h fasting with either 6 (6 h pre+18 h post) or 12 h (12 h pre+12 h post-) of feed restriction prior to treatment, 12 h fasting either prior to (12 h pre-) or post (12 h post) treatment. In Experiment II, calves from the same pool of animals were subjected to a 24 h fasting period prior to the same ABZ treatment and killed (two animals) at either 24, 36 or 48 h post-administration to obtain samples of abomasal/intestinal mucosa and fluid contents, bile and lungs. Plasma (Experiment I) and tissues/fluids (Experiment II) samples were analysed by HPLC. All the fasting periods investigated induced marked changes to the plasma availability and disposition kinetics of the ABZSO metabolite. Enhanced plasma availability between 37 and 118%, delayed peak concentrations and extended mean residence times for ABZSO were observed in fasted compared to fed calves. The changes in plasma kinetics, reflecting an altered quantitative gastrointestinal absorption, were reflected in increased availability of ABZ and ABZSO in the target tissues/fluids of fasted calves. The availabilities of ABZ and ABZSO in the gastrointestinal mucosa and fluids in fasted calves were markedly greater than in those fed ad libitum. [source]

Mira variables in the Galactic bulge with OGLE-II data

MONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 1 2005
Noriyuki Matsunaga
ABSTRACT We have extracted a total of 1968 Mira variables from the Optical Gravitational Lensing Experiment II (OGLE-II) data base in the Galactic bulge region. Among them, 1960 are associated with 2 Micron All-sky Survey (2MASS) sources, and 1541 are further identified with Midcourse Space Exploration (MSX) point sources. Their photometric properties are compared with those of Mira variables in the Large and Small Magellanic Clouds. We have found that mass-losing stars with circumstellar matter are reddened such that the colour dependence of the absorption coefficient is similar to that of interstellar matter. We also discuss the structure of the bulge. The surface number density of the bulge Mira variables is well correlated with the 2.2-,m surface brightness obtained by the Cosmic Background Explorer (COBE) satellite. Using this relation, the total number of Mira variables in the bulge is estimated to be about 6 × 105. The log P,K relation of the Mira variables gives their space distribution which supports the well-known asymmetry of the bar-like bulge. [source]

Assessment of Progesterone Concentration Using Enzymeimmunoassay, for Early Pregnancy Diagnosis in Sheep and Goats

REPRODUCTION IN DOMESTIC ANIMALS, Issue 3 2003
CM Boscos
Contents The objective of this study was to determine a value of serum progesterone (P4) concentration, assessed using an enzymeimmunoassay (EIA), for the early distinction between pregnant and non-pregnant ewes and goats. Adult, non-lactating ewes of Chios (n=53), Berrichon (n=30) and Sfakia (n=45) breeds were synchronized during the breeding season with progestagens and gonadotrophins and mated to fertile rams (Experiment I). Adult, lactating goats of Swiss breeds (Alpine and Saanen, n=104) and indigenous Greek breed (n=45) were synchronized during the transitional season with progestagens, PGF2, and gonadotrophins. Cervical artificial insemination (AI) with fresh semen was applied once, 42,44 h after sponge removal (Experiment II). Jugular blood samples were collected on day 19 after sponge removal (ewes) or on day 21 after AI (goats) and serum P4 concentration was determined by EIA. Progesterone concentrations ,1.0, ,1.5, ,2.5 and ,4.0 ng/ml were tested as indicative of pregnancy. Pregnancy diagnosis was verified on birth. In the case of sheep, using a discriminatory level of 2.5 ng/ml, overall accuracy of pregnancy diagnosis was 91.4% and predictive value of negative and positive diagnoses were 98.3 and 85.3%, respectively. In the case of goats, predictive value of negative diagnosis was 95.8 and 94.0% and predictive value of positive diagnosis 71.3 and 71.7%, for 1.5 and 2.5 ng/ml, respectively; overall accuracy was 79.2% using either level. The other discriminatory levels tested did not improve these results. A significant positive correlation was observed between P4 concentration and the number of lambs or kids born, and further analysis indicated that this relationship is not a simple linear function. Based on the results of this study, P4 concentrations of 2.5 ng/ml in the case of ewes and 1.5,2.5 ng/ml in the case of goats, determined with EIA, are proposed as discriminatory levels between pregnant and non-pregnant animals, at an interval of one oestrous cycle after service. [source]

Effects of boning method and postmortem aging on meat quality characteristics of pork loin

ANIMAL SCIENCE JOURNAL, Issue 5 2009
Chunbao LI
ABSTRACT This work investigated the effects of boning method and postmortem aging on pork loin color, shearing value and sensory attributes. Two experiments were assigned. In Experiment I, 30 Chinese native black pigs were slaughtered and their carcasses were divided into three groups: (i) hot-boning: carcasses were fabricated within 45 min postmortem just after dressing; (ii) cold boning at 24 h: carcasses were fabricated after chilling at 0°C for 24 h; (iii) cold boning at 36 h: carcasses were fabricated after chilling at 0°C for 36 h. In Experiment II, right sides of the second group in Experiment I were used and primal cuts were vacuum packed and aged for 1 day, 8 days and 16 days. Pork loins (Longissimus lumborum) were used for color measurement, shearing test, and sensory evaluation. Among three boning methods, cold-boning at 36 h postmortem had the advantages of giving muscles a better color, the lowest cooking loss and cooked shearing value, and the highest sensory tenderness, juiciness, flavor and overall liking. Postmortem aging could improve pork quality characteristics, but it is not the fact that the longer aging time is, the better pork quality would be. Eight days may be enough to obtain an acceptable sensory attribute. These results are meaningful for pork processing and pork consumption. [source]

Absence of corneal endothelium injury in non-human primates treated with and without ophthalmologic drugs and exposed to 2.8,GHz pulsed microwaves,,

BIOELECTROMAGNETICS, Issue 4 2010
Shin-Tsu Lu
Abstract Microwave-induced corneal endothelial damage was reported to have a low threshold (2.6,W/kg), and vasoactive ophthalmologic medications lowered the threshold by a factor of 10,0.26,W/kg. In an attempt to confirm these observations, four adult male Rhesus monkeys (Macaca mulatta) under propofol anesthesia were exposed to pulsed microwaves in the far field of a 2.8,GHz signal (1.43,±,0.06,µs pulse width, 34,Hz pulse repetition frequency, 13.0,mW/cm2 spatial and temporal average, and 464,W/cm2 spatial and temporal peak (291,W/cm2 square wave equivalent) power densities). Corneal-specific absorption rate was 5.07,W/kg (0.39,W/kg/mW/cm2). The exposure resulted in a 1.0,1.2,°C increase in eyelid temperature. In Experiment I, exposures were 4,h/day, 3 days/week for 3 weeks (nine exposures and 36,h total). In Experiment II, these subjects were pretreated with 0.5% Timolol maleate and 0.005% Xalatan® followed by 3 or 7 4-h pulsed microwave exposures. Under ketamine,xylazine anesthesia, a non-contact specular microscope was used to obtain corneal endothelium images, corneal endothelial cell density, and pachymetry at the center and four peripheral areas of the cornea. Ophthalmologic measurements were done before and 7, 30, 90, and 180 days after exposures. Pulsed microwave exposure did not cause alterations in corneal endothelial cell density and corneal thickness with or without ophthalmologic drugs. Therefore, previously reported changes in the cornea exposed to pulsed microwaves were not confirmed at exposure levels that are more than an order of magnitude higher. Bioelectromagnetics 31:324,333, 2010. Published 2010 Wiley-Liss, Inc. [source]

Effect of different liquid cultures of live yeast strains on performance, ruminal fermentation and microbial protein synthesis in lambs

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 6 2008
M. K. Tripathi
Summary Three yeast strains, Kluyveromyces marximanus NRRL-3234 (KM), Saccharomyces cerevisiae NCDC-42 (SC) and Saccharomyces uvarum ATCC-9080 (SU), and a mixed culture (1:1:1 ratio) were evaluated for their value as probiotics in lamb feeding in two experiment. In experiment I and II, 20 and 30 pre-weaner lambs were fed for 63 and 60 days in two and three equal groups respectively. All lambs were offered ad libitum a creep mixture and Zizyphus nummularia leaves, and yeasts were dosed orally. In experiment I, one group received no yeast, the other of the mixed culture (1.5,2 × 1010 live cells/ml). In experiment II, yeast cultivation was modified yielding 1.5,2 × 1013 live cells/ml. Lambs of the three experimental groups received 1 ml/kg live weight of one of the individual yeasts. Feed intake did not differ among groups of both experiments with the exception of SC-supplemented lambs in experiment II which showed a trend to higher intakes per kg metabolic body weight and in percentage of body weight when compared with KM- and SU-supplemented lambs. Supplementation of the mixed yeast culture had no effect on intakes of digestible crude protein and metabolisable energy, nutrient digestibility, nitrogen balance and rumen fermentation characteristics (pH, ammonia, volatile fatty acid concentration, protozoa count) and urinary allantoin as an indicator of microbial protein synthesis. The same was true for comparisons in experiment II except ciliate protozoa counts, which showed a trend to be the highest with SU and the lowest with SC. The results of present study show that the response of lambs to supplemented live yeast cultures is inconsistent, as it lacked to have an effect in the present study, and that differences among strains were small, even when supplemented at a much higher live cell count. [source]

Intraperitoneal injection of d- galactosamine provides a potent cell proliferation stimulus for the detection of initiation activities of chemicals in rat liver

JOURNAL OF APPLIED TOXICOLOGY, Issue 6 2005
Yoshiji Asaoka
Abstract In an in vivo 5-week initiation assay model, chemical hepatectomy by hepatotoxicant administration was utilized as a cell proliferation stimulus as an alternative to the two-thirds partial hepatectomy. The study investigated the effect of an intraperitoneal (i.p.) injection of d- galactosamine (d -gal) for this purpose in a medium-term liver bioassay, with a further focus on cell proliferation kinetics and cytochrome P450 (CYP) expression. In experiment I, cell proliferation in rat liver after a single administration of d -gal (700 mg kg,1, i.p.) was analysed by the bromodeoxyuridine (BrdU) labeling method, and CYP isozymes were quantified by immunoblotting. In experiment II, the induction of glutathione S-transferase placental form (GST-P) positive foci by 1,2-dimethylhydrazine (DMH) was evaluated in a modified in vivo 5-week initiation assay model. At 84 hours after single administration of d -gal (i.p.) the BrdU index was markedly elevated (27.5% ± 9.5%). Although CYP 2E1 and 1A2 apoprotein contents decreased transiently to less than 20% of the control level, subsequently they recovered to 60% and 40% of the control level, respectively, at 84 hours. Induction of GST-P positive foci in the group given DMH at 84 hours after a single administration of d -gal was significantly greater than in the control group, correlating with the kinetics of cell proliferation. In conclusion, the sensitivity of the present initiation assay using d -gal i.p. is high, so that d -gal i.p. can be considered an effective cell proliferation stimulus. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Tower Climbing Exercise Started 3 Months After Ovariectomy Recovers Bone Strength of the Femur and Lumbar Vertebrae in Aged Osteopenic Rats,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2003
Takuya Notomi
Abstract To determine both the preventive and recovery effects of tower climbing exercise on mass, strength, and local turnover of bone in ovariectomized (OVX) rats, we carried out two experiments. In experiment I, 60 Sprague-Dawley rats, 12 months of age, were assigned to four groups: a Baseline Control, Sham-Operated Sedentary, OVX-Sedentary and OVX-Exercise rats. Rats voluntarily climbed a 200-cm tower to drink water from a bottle set at the top. At 3 months, OVX elevated both the femoral cortex and lumbar trabecular turnover, leading to a reduction in bone mass and strength. However, in OVX-Exercise rats, those values were maintained at the same level as in the Sham-Sedentary rats. Thus, the climbing exercise, started after 3 days of OVX, prevented OVX-induced cortical and trabecular bone loss by depressing turnover elevation. After confirming the preventive effect, we evaluated the recovery effect of exercise. In experiment II, 90 Sprague-Dawley rats, 12 months of age, were assigned to six groups: a Baseline control, two groups of Sham-Operated Sedentary and OVX-Sedentary, and OVX-Exercise rats. The exercise started 3 months after the OVX operation. At 3 months, OVX increased the trabecular bone formation rate and osteoclast surface, leading to a decrease in compressive strength. In the midfemur, the cross-sectional area, moment of inertia, and bending load values decreased. At 6 months, in the OVX-Exercise rats, the parameters of breaking load in both the lumbar and midfemur, lumbar bone mass, and the total cross-sectional area recovered to the same levels as those in the Sham-Sedentary rats. However, the cortical bone area did not recover. Periosteal bone formation increased, while endosteal bone formation decreased. These results showed that the climbing exercise had both a preventive and recovery effect on bone strength in OVX rats. In the mid-femur, effects on bone formation were site-specific, and the cross-sectional morphology was improved without an increase in cortical bone area, supporting cortical drift by mechanical stimulation. [source]

SUCROSE DETECTION AND THE STABILITY OF THE 2-AFC PROCEDURE IN THE PRESENCE OF A CONFOUNDING VARIABLE

JOURNAL OF SENSORY STUDIES, Issue 5 2008
DANIEL SHEPHERD
ABSTRACT This study attempted to measure absolute thresholds for sucrose in aqueous solution for 51 experienced judges. Two experiments utilizing the two-alternative forced-choice (2-AFC) procedure generated 6-point psychometric functions plotting percentage correct as a function of sucrose concentration. In both experiments, the judges were divided into two groups and tested in either purpose-built sensory booths or on open tables situated in a laboratory. In the first experiment, the influence of a confounding variable was apparent, with nonmonotonic psychometric functions being obtained. In experiment II, the confounding variable was eliminated, permitting the estimation of absolute thresholds. In both experiments, there was no main effect of gender or session, though there was an effect of testing locality (P < 0.05). Data are reported to emphasize the importance of controlling extraneous variables and to demonstrate the robustness of the 2-AFC procedure. PRACTICAL APPLICATIONS This research contributes to an otherwise impoverished database on the detection of sucrose in a solution. The uses of the research include estimates of sucrose detection thresholds for comparative purposes; confirmation of the stability of the two-alternative forced-choice procedure; the utility of using formal testing areas as opposed to ad hoc testing stations; and the dangers of utilizing substandard experimental equipment while conducting research of this nature. [source]

SIMULTANEOUS ESTIMATIONS OF MULTIPLE PRODUCT SIMILARITIES USING A NEW DISCRIMINATION PROTOCOL

JOURNAL OF SENSORY STUDIES, Issue 5 2007
BENOÎT ROUSSEAU
ABSTRACT This research investigated new paradigms that permit the simultaneous comparison of more than two samples in a discrimination study. Three successive experiments were conducted. All involved noncarbonated orange beverages. In experiment I, Torgerson's method of triads was found to be more discriminating than the multiple dual-pair method and was used in the subsequent two experiments. In experiments II and III, subjects discriminated among stimuli using the Torgerson's method as well as traditional duo,trios. In experiment II, the univariate Thurstonian model with four distributions was found to provide a suitable fit of the data, and the d, values obtained using the traditional duo,trio methodology were not found to be significantly different from those obtained with Torgerson's method. In experiment III, a multivariate, but not univariate, model provided a good fit of the data. Furthermore, d, values from the Torgerson's method were not found to be significantly different from those obtained using the traditional duo,trio methodology. PRACTICAL APPLICATIONS This research supported the use of a Thurstonian model for Torgerson's method of triads and uncovered the usefulness of the method when comparing more than two samples using a discrimination methodology, which has applications in situations involving samples with inherent intra-product variations. Flexibility in the models available also permits the estimation of the dimensionality of the differences among the stimuli involved, providing valuable information that can be obtained more efficiently than running multiple pair-wise traditional discrimination trials. [source]

Chronic Intermittent Injections of High-Dose Ethanol During Adolescence Produce Metabolic, Hypnotic, and Cognitive Tolerance in Rats

ALCOHOLISM, Issue 10 2003
Janelle M. Silvers
Background: Many humans are first exposed to ethanol during adolescence, the time at which they are most likely to binge drink ethanol. Chronic intermittent ethanol (CIE) exposure produces ethanol tolerance in adolescent rodents. Recent studies suggested that adolescent animals administered CIE experienced increased cognitive impairment following an ethanol challenge. These studies further explore development of ethanol tolerance caused by CIE in adolescence, and whether CIE during adolescence leads to altered ethanol response in adulthood. Methods: Beginning postnatal day (P) 30, adolescent rats were administered 5.0 g/kg ethanol or saline every 48 hours for 20 days. In experiment I, animals were tested for differential weight gain. In experiment II, loss of righting reflex (LORR) was observed after each injection, then at completion of pretreatment all animals were tested with 5.0 g/kg ethanol and LORR was observed. In experiment III, blood ethanol levels were observed and elimination rates calculated after the first and fifth pretreatments. All animals were tested with 5.0 g/kg at completion of pretreatment and elimination rates were recalculated. In experiment IV, animals were trained on the spatial version of the Morris Water Maze Task (MWMT) on non-treatment days. Following completion of pretreatment and training, animals were tested after receiving an ethanol (1.0, 1.5, or 2.0 g/kg), or saline. Tests for experiments II, III, and IV were repeated in the same animals following 12 ethanol-free days. Results: Chronic intermittent ethanol exposure during adolescence caused differential weight gain (experiment I). Adolescent rats developed tolerance to ethanol-induced LORR (experiment II) and metabolic tolerance to ethanol (experiment III). This tolerance was seen after 12 ethanol-free days. CIE also attenuated ethanol-induced spatial memory deficits in the MWMT (experiment IV). This effect was not long-lasting. Conclusions: Following CIE pretreatment during adolescence, tolerance developed to the hypnotic and cognitive impairing effects of ethanol, along with increased metabolic rate and decreased weight gain. These results further emphasize the ability of CIE to produce a variety of effects during adolescence, some having long-lasting consequences. [source]

Pharmacokinetic,pharmacodynamic modelling of the analgesic effects of lumiracoxib, a selective inhibitor of cyclooxygenase-2, in rats

BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2010
DA Vásquez-Bahena
Background and purpose:, This study establishes a pharmacokinetic/pharmacodynamic (PK/PD) model to describe the time course and in vivo mechanisms of action of the antinociceptive effects of lumiracoxib, evaluated by the thermal hyperalgesia test in rats. Experimental approach:, Female Wistar fasted rats were injected s.c. with saline or carrageenan in the right hind paw, followed by either 0, 1, 3, 10 or 30 mg·kg,1 of oral lumiracoxib at the time of carrageenan injection (experiment I), or 0, 10 or 30 mg·kg,1 oral lumiracoxib at 4 h after carrageenan injection (experiment II). Antihyperalgesic responses were measured as latency time (LT) to a thermal stimulus. PK/PD modelling of the antinociceptive response was performed using the population approach with NONMEM VI. Results:, A two-compartment model described the plasma disposition. A first-order model, including lag time and decreased relative bioavailability as a function of the dose, described the absorption process. The response model was: LT=LT0/(1 +MED). LT0 is the baseline response, and MED represents the level of inflammatory mediators. The time course of MED was assumed to be equivalent to the predicted profile of COX-2 activity and was modelled according to an indirect response model with a time variant synthesis rate. Drug effects were described as a reversible inhibition of the COX-2 activity. The in vivo estimate of the dissociation equilibrium constant of the COX-2-lumiracoxib complex was 0.24 µg·mL,1. Conclusions:, The model developed appropriately described the time course of pharmacological responses to lumiracoxib, in terms of its mechanism of action and pharmacokinetics. [source]

Differential Effects of Partial Hepatectomy and Carbon Tetrachloride Administration on Induction of Liver Cell Foci in a Model for Detection of Initiation Activity

CANCER SCIENCE, Issue 10 2001
Hiroki Sakai
Differential effects of partial hepatectomy (PH) and carbon tetrachloride (CC14) administration on induction of glutathione S-transferase placental form (GST-P)-positive foci were investigated in a model for detection of initiation activity. Firstly, we surveyed cell proliferation kinetics and fluctuation in cytochrome P450 (CYP) mRNA levels by means of relative-quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and CYP 2E1 apoprotein amount by immuno-blotting (experiment I) after PH or CC14 administration. Next, to assess the interrelationships among cell proliferation, fluctuation of CYPs after PH or CC14 administration and induction of liver cell foci, the non-hepatocarcinogen, 1,2-dimethylhydrazine (DMH) was administered to 7-week-old male F344 rats and initiated populations were selected using the resistant hepatocyte model (experiment II). In experiment I, the values of all CYP isozyme mRNAs after PH or CC14 administration were drastically decreased at the 12-h tune point. From 72 h, mRNAs for all CYP isozymes began increasing, with complete recovery after 7 days. The CYP 2E1 apoprotein content in the PH group fluctuated weakly, whereas in the CC14 group it had decreased rapidly after 12 h and was still low at the 48 h point. In experiment II, induction of GST-P-positive foci was related to cell kinetics in the PH group, with about a 6-h time lag between tune for carcinogen administration giving greatest induction of GST-P-positive foci and peaks in bromodeoxyuridine (BrdU) labeling, presumably due to the necessity for bioactivation of DMH. With CC14 administration, induction of foci appeared dependent on the recovery of CYP 2E1. In conclusion, PH was able to induce cell proliferation with maintenance of CYP 2E1, therefore being advantageous for induction of liver cell foci in models to detect initiation activity. [source]