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Role of energy metabolism in the pregnancy interceptive action of Ferula assafoetida and Melia azedarach extracts in rat.

Ethanolic extract of Ferula assafoetida and chloroform fraction of Melia azedarach, both devoid of estrogenic activity, were examined for their pregnancy interceptive property. Treatment of rats from days 1 to 7 of pregnancy with either of the plant extracts resulted in pregnancy failure in about 65-85% of the animals. The possible role of energy metabolism in the antifertility action was investigated by measuring changes in activities of the key enzymes of carbohydrate metabolism in uterus on day 7 of pregnancy. It was observed that on the day 7 of pregnancy, one key enzyme of glycolytic pathway (phosphofructokinase) was significantly reduced in the uteri of treated rats as compared to controls. Hexosemonophosphate pathway also appeared to be sensitive to treatment with the plant extracts and showed an inhibitory effect on the enzyme activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Oxidative energy metabolism through tricarboxylic acid cycle, which is considered to be the main source of energy to the uterus at this stage, was maximally affected by the treatment with several enzymes showing significant inhibition. The two plant materials appeared to interrupt the latter metabolic pathway more significantly. It is thus concluded that plants lacking phytoestrogens may intercept pregnancy by their ability to disrupt energy metabolism in rat uterus during implantation, especially the oxidative pathway.

Animals↗

Target-oriented anti-implantation approaches for pregnancy interception: experiences in the rhesus monkey model.

Blastocyst implantation is a critical process in the establishment of pregnancy in eutherian mammals and requires a harmonious symbiosis between the developing conceptus and the differentiating maternal uterus. A better understanding of this symbiotic relationship will provide novel approaches and interventions for realizing anti-implantation strategies for effective fertility regulation and reproductive health care management. We have been using the rhesus monkey (Macaca mulatta) as a nonhuman primate model to this end. In the present study, the process of progesterone-mediated regulation of endometrial receptivity for blastocyst implantation has been targeted by the use of mifepristone as an emergency contraceptive agent. Furthermore, based on cell-specific, temporal and spatial distribution of vasotropic cytokines and mediators in the "receptive" and periimplantation periods, the pregnancy interceptive potentials of (a) monoclonal antibody (MAb) to leukemia inhibitory factor (LIF); (b) inhibitors of nitric oxide synthase [e.g., N6-nitro-l-arginine (l-NAME) and aminoguanidine]; and (c) MAb to vascular endothelial growth factor (VEGF) were examined. LIF is a progesterone-responsive pleiotropic cytokine that functions as a proinflammatory cytokine, together with interleukins 1 and 6, during the process of implantation-placentation in primates, and its immunoneutralization with MAb resulted in inhibition (p<.04) of pregnancy establishment in the rhesus monkey. However, timed administration of l-NAME or aminoguanidine failed to inhibit blastocyst implantation in a significant manner. Also, no synergistic antinidatory action of antiprogestin combined with l-NAME was detected in the rhesus monkey. The application of MAb to VEGF during the periimplantation period, on the other hand, led to significant (p<.04) prevention of pregnancy without influencing steroid hormone levels in the circulation. Our data lend support to the hypothesis that VEGF is essential for pregnancy establishment and that trophoblast-derived VEGF, acting via its specific receptors Flt-1 and KDR, is necessary for blastocyst implantation. The use of cDNA-based expression arrays followed by differential display analysis has provided preliminary understanding of the nature of gene cluster networks operative in the receptive endometrium of potential conception cycles in the rhesus monkey. This knowledge may, in the future, lead to further innovative anti-implantation strategies for targeted pregnancy interception.

Animals↗

The impact of task-constraints on the planning and control of interceptive hitting movements.

On the basis of research in self-paced aiming movements, Glover [S. Glover, Separate visual representations in the planning and control of action, Behav. Brain Sci., 27 (2004) 3-24] proposed a dichotomy between visual systems that accommodate planning and on-line control of action. Specifically, the planning-versus-control model posits that the on-line control system solely adjusts the spatial parameters of a movement. We examined whether this proposition is also adequate for interceptive hitting movements that require being at a specific location at the right time. Participants had to hit an approaching ball by first moving the bat away from the interception point (preparatory phase) and subsequently make the hitting movement (strike phase). The ball had to be projected to a landing location that could be near or far. To examine the ability of actors to use online visual information to adapt to unexpected changes in impact requirements, we perturbed the distance of the landing location from near to far during the unfolding of the movement. No adjustments were observed when the perturbation occurred at the onset of the strike phase. When the perturbation occurred at the onset of the preparatory phase the impact velocity increased and, therefore, the ball traveled a larger distance. This was realized by decreasing the duration of the strike phase and increasing the movement amplitude. So, both spatial and temporal characteristics of the hitting movement were adjusted to comply with an online perturbation of target distance. This observation is incongruent with Glover's recent proposition that the online visual system only accommodates spatial parameters.

Adult↗

Effects of acoustic startle stimuli on interceptive action.

In reaction time (RT) tasks, presentation of a startling acoustic stimulus (SAS) together with a visual imperative stimulus can dramatically reduce RT while leaving response execution unchanged. It has been suggested that a prepared motor response program is triggered early by the SAS but is not otherwise affected. Movements aimed at intercepting moving targets are usually considered to be similarly governed by a prepared program. This program is triggered when visual stimulus information about the time to arrival of the moving target reaches a specific criterion. We investigated whether a SAS could also trigger such a movement. Human experimental participants were trained to hit moving targets with movements of a specific duration. This permitted an estimate of when movement would begin (expected onset time). Startling and sub-startle threshold acoustic probe stimuli were delivered unexpectedly among control trials: 65, 85, 115 and 135 ms prior to expected onset (10:1 ratio of control to probe trials). Results showed that startling probe stimuli at 85 and 115 ms produced early response onsets but not those at 65 or 135 ms. Sub-threshold stimuli at 115 and 135 ms also produced early onsets. Startle probes led to an increased vigor in the response, but sub-threshold probes had no detectable effects. These data can be explained by a simple model in which preparatory, response-related activation builds up in the circuits responsible for generating motor commands in anticipation of the GO command. If early triggering by the acoustic probes is the mechanism underlying the findings, then the data support the hypothesis that rapid interceptions are governed by a motor program.

Acoustic Stimulation↗

The combined effect of platelet storage media and intercept pathogen reduction technology on platelet activation/activability and cellular apoptosis/necrosis: Lisbon-RBS experience.

Platelets are known to undergo shape change, activation, a release reaction and apoptosis/necrosis during processing and storage, all of which are collectively known as the platelet storage lesion. Any additional processing may have some deleterious impact on platelet activability and functional integrity, which need to be investigated. This preliminary investigation was undertaken to establish the combined effects of standard platelet storage media and the intercept pathogen reduction technology on platelet activation and activability during 7 day storage, using buffy-coat derived platelets in standard storage media containing 35% plasma (N=24). P-selectin (CD62p) expression, a classical marker of platelet activation, and phosphatidylserine (PS) exposure on the platelet surface membrane, a hallmark of cellular necrosis/apoptosis, were both measured by flow cytometry. The results reveal significant increases in activation, from an average of 22.7% on day 1 before treatment to 31.6% on day 2 after treatment and 58.7% at the end of storage. Concomitantly, the basal expression of PS was slightly increased from 1.9% to 2.8% at day 2 after treatment and 7.3% at the end of storage. However, the functional reserve of platelets during storage, which reflects their capability to undergo activation and the release reaction when platelets were challenged with either calcium ionophore or thrombin, was relatively well maintained. These preliminary data confirm the earlier data on the use of intercept, and for the first time, based on the assessment of platelet functional integrity, suggest that platelet functional reserve is relatively well maintained, with little change in the formation of apoptotic cells.

Apoptosis↗

Prospective control of manual interceptive actions: comparative simulations of extant and new model constructs.

Two prospective controllers of hand movements in catching-both based on required velocity control-were simulated. Under certain conditions, this required velocity control led to overshoots of the future interception point. These overshoots were absent in pertinent experiments. To remedy this shortcoming, the required velocity model was reformulated in terms of a neural network, the Vector Integration To Endpoint model, to create a Required Velocity Integration To Endpoint model. Addition of a parallel relative velocity channel, resulting in the Relative and Required Velocity Integration To Endpoint model, provided a better account for the experimentally observed kinematics than the existing, purely behavioral models. Simulations of reaching to intercept decelerating and accelerating objects in the presence of background motion were performed to make distinct predictions for future experiments.

Biomechanical Phenomena↗

Random intercept item factor analysis.

The common factor model assumes that the linear coefficients (intercepts and factor loadings) linking the observed variables to the latent factors are fixed coefficients (i.e., common for all participants). When the observed variables are participants' observed responses to stimuli, such as their responses to the items of a questionnaire, the assumption of common linear coefficients may be too restrictive. For instance, this may occur if participants consistently use the response scale idiosyncratically. To account for this phenomenon, the authors partially relax the fixed coefficients assumption by allowing the intercepts in the factor model to change across participants. The model is attractive when m factors are expected on the basis of substantive theory but m + 1 factors are needed in practice to adequately reproduce the data. Also, this model for single-level data can be fitted with conventional software for structural equation modeling. The authors demonstrate the use of this model with an empirical data set on optimism in which they compare it with competing models such as the bifactor and the correlated trait-correlated method minus 1 models.

Factor Analysis, Statistical↗

Target speed alone influences the latency and temporal accuracy of interceptive action.

When intercepting a mobile object or an apparent movement, participants show a temporal bias. They are in advance when dealing with a slow-moving stimulus and late with a fast-moving one. We studied participants intercepting an apparent movement by sliding a disk on a table. Using a fast and a slow stimulus speed, we varied three factors: duration of presentation of the stimulus, distance covered by the stimulus, and speed context (constant or varied) of stimulus presentation. In addition to the temporal bias, spatial accuracy and kinematic measures were collected. The temporal bias created by speed was evident across all three factors. Speed, in addition to strongly determining the temporal bias, significantly affected the throwing strategy adopted by the participants, as revealed by latency, movement time, and disk trajectory duration.

Adult↗

Specificity of practice in a ball interception task.

Learning of an aiming task has been shown to be specific to the sources of afferent information available during practice. However, this has not been the case when a one-hand ball-catching task has been used. The goal of the present study was to determine the cause of these conflicting results. Participants practiced an interception task in either a normal vision condition or a ball-only condition. They were all then transferred to the ball-only condition, using either the same ball trajectories as in acquisition or different ones. Being transferred from a normal vision condition to a ball-only condition resulted in a significant increase in spatial interception errors, thus supporting the specificity of practice hypothesis. Using new ball trajectories in transfer caused a significant increase in error for all participants. The pattern of errors observed when new ball trajectories were used suggests that participants had difficulty correlating information about the location of their arm via proprioception and a combination of retinal and extra-retinal information about the ball trajectory.

Analysis of Variance↗

Legionella phagosomes intercept vesicular traffic from endoplasmic reticulum exit sites.

It is unknown how Legionella pneumophila cells escape the degradative lysosomal pathway after phagocytosis by macrophages and replicate in an organelle derived from the endoplasmic reticulum. Here we show that, after internalization, L. pneumophila-containing phagosomes recruit early secretory vesicles. Once L. pneumophila phagosomes have intercepted early secretory vesicles they begin to acquire proteins residing in transitional and rough endoplasmic reticulum. The functions of Sar1 and ADP-ribosylation factor-1 are important for biogenesis of the L. pneumophila replicative organelle. These data indicate that L. pneumophila intercepts vesicular traffic from endoplasmic-reticulum exit sites to create an organelle that permits intracellular replication and prevents destruction by the host cell.

Animals↗

Preclinical safety profile of plasma prepared using the INTERCEPT Blood System.

BACKGROUND AND OBJECTIVES: The newly developed INTERCEPT Blood System for plasma uses the addition of a new psoralen, amotosalen HCl (AMOTOSALEN), followed by illumination with ultraviolet A light, to inactivate viruses, bacteria, protozoa and leucocytes that may contaminate fresh-frozen plasma (FFP). Extensive toxicology studies were performed to characterize the safety of the photochemical treatment process for its intended use with plasma. MATERIALS AND METHODS: The studies of general toxicology, safety pharmacology, phototoxicity, reproductive toxicity and venous irritation, summarized in this review, provide a comprehensive toxicology profile for photochemically treated 100% plasma. RESULTS: No specific target organ toxicity (based on clinical or histological pathology), phototoxicity, or reproductive toxicity was observed. CONCLUSIONS: The results of an extensive series of studies have demonstrated no toxicologically relevant effects of photochemically treated 100% plasma prepared using the INTERCEPT Blood System for plasma.

Animals↗

Interceptive activities of STS 557 in rabbits, mice and rats.

STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) is a interceptive agent in rabbits, mice and rats. In rats, it also shows post-implantational pregnancyterminating activity. In rabbits treated orally before mating or after ovulation for three consecutive days, it inhibited pregnancy largely at total doses of 0.08 mg/kg in the former and completely with 8.0 mg/kg in the latter case. A single subcutaneous dose of 40 mg/kg given on day 1 of pregnancy inhibited completely nidation in rats. In inhibition of pregnancy in rats could also be realized when the dose of 40 mg/kg was distributed on several days and given subcutaneously at daily doses of 5.0 mg/kg on days 1--8 of pregnancy, and even only daily doses of 2 mg STS 557/kg were needed in this respect, if animals which showed no living conceptuses were scored as "non-pregnant". STS 557 was effective in terminating pregnancy in rats, too, when given subcutaneously after implantation for 4 days at daily doses of 50 mg/kg, beginning on day 5 or on day 8 of pregnancy. The nidation inhibiting effects of STS 557 in rabbits treated pre-coitally, and in mice as well as in rats treated post-coitally were more marked than those of levonorgestrel. The interceptive and post-implantational inhibiting activity of STS 557 may be based on its antiprogestagenic properties. Luteolysis in the nidation phase can be excluded as shown by radioimmunoassay of progesterone in rats. The antigestagenic effects on the endometrium in rats were evident in the diamine oxidase assay. The acceleration of tubal egg transport, the morphological changes of the endometrium shown by scanning electron microscopy, and the effects on blastocyst transfer, all investigated in rats, suggest peripheral mechanisms of action.

Amine Oxidase (Copper-Containing)↗

[New approaches to interception--postcoital use of a gestagen/estrogen combination].

Postcoital application of high doses of ethenyloestradiol (EE) over a period of 5-6 days can, in the majority of cases, prevent pregnancy if therapy is initiated early enough (failure rate 1%), but such doses are attended by a high rate of side effects. Yuzpe et al. have tested an alternative formulation for interception: in a series of studies conducted in Canada and USA they administered a total dose of only 0.2 mg EE in combination with 2.0 mg DL-norgestrel (potency equivalent to a dose of 1.0 mg D-norgestrel) which was given in 2 portions separated by a 12-hour interval. The results of these studies and, in particular, those of a double-blind study (high doses of EE versus EE/norgestrel combination) in the Netherlands appear to indicate that the interceptive efficacy of the oestrogen-gestagen combination is equivalent to that of the high-dose oestrogen formulation. Distinct advantages are: the much lower active substance content, the shorter period of therapy (12 hours as opposed to 5 days), which is important as regards patient compliance, the limited duration of concomitant gastro-intestinal effects which can no longer be responsible for premature termination of therapy, the absence of breast tension and menstrual disorders. However, even application of the new method, which is facilitated by the commercial preparation Tetragynon, is intended for emergencies only.

Contraceptives, Postcoital↗

Importance of uterine expulsion of embryos in the interceptive mechanism of postcoital oestradiol in rats.

This study compares the interceptive effectiveness of 1 microgram oestradiol given as a single s.c. injection at 0900 or 1700 hours on Day 1, 2, 3, or 4 of pregnancy in rats. Increasing the interval from ovulation to treatment accelerated the oviducal transport of a larger number of embryos, the majority of which were lost from the genital tract. However, after treatment at 1700 hours on Day 3 the majority of accelerated embryos were retained in the uterus. The number of implanted embryos on Day 14 was equal to the number of eggs remaining in the tract 24 h after treatment. As a consequence, the highest interceptive effectiveness was obtained with treatment given at 1700 hours on Day 2 and at 0900 hours on Day 3 of pregnancy. Accelerated oviducal transport and uterine expulsion of embryos begin to dissociate after Day 2 of pregnancy in the rat. This explains why the most effective treatments to accelerate oviducal transport are not always the most effective to reduce the number of implantations. These data emphasize the importance of retentive and expulsive properties of the uterus for fertility and infertility.

Animals↗

Rate of change of angular bearing as the relevant property in a horizontal interception task during locomotion.

The authors ran 3 experiments to investigate how catchers deal with the horizontal component of the ball's trajectory in an interception task during locomotion. The experiments were built upon the finding that velocity adaptations are based upon changes in the horizontal angular position or velocity of the ball with respect to the observer (M. Lenoir, M. Janssens, E. Musch, E. Thiery, J. Uyttenhove, 1999) a potential underlying information source for that strategy is described. In Experiment 1, actor (N = 10 participants)and ball approached each other along the legs of a V-shaped track. When the velocity and the initial angular bearing of the ball were varied, the observed behavior fitted with nulling the horizontal angular velocity of the ball: A positive or negative angular velocity was compensated by a velocity change. Evidence was obtained that those adaptations are modulated by a critical change in, rather than by a critical state of, the environment-actor system. In Experiment 2, the distance between the head and an artificial end-effector was varied. Irrespective of that distance, participants (N = 7) accelerated and decelerated in order to keep the angular velocity of the ball with respect to the end-effector close to constant. The ecological relevance of that constant bearing angle strategy was confirmed in Experiment 3: Participants (N = 7) in that experiment freely ran to catch fly balls. The present results support the concept that one can explain with a limited number of control variables an actor's behavior in an interception task during self-motion.

Adult↗

Intercepting moving objects during self-motion: effects of environmental changes.

The purpose of this study was to examine the role of background texture on an interception task during self-motion. Twenty-six participants modulated tricycle speed along one arm of a V-shaped track so as to intercept a ball approaching horizontally on the other arm of the V. Either a plain or a textured background (consisting of contrasting vertical stripes) was used. Velocity modulations occurred so as to keep the angle beta between the direction of heading and the line head-ball constant (constant bearing angle, or CBA strategy), indicating that this observer-environment relation might regulate the approach phase. In the textured condition, participants initially drove faster than predicted by the CBA model and compensated by slowing down in the second half. This is in line with the texture-induced overestimation of the ball velocity and implies that absolute velocity information is also used.

Analysis of Variance↗

Effect of ozone on mean linear intercept in the lung of young beagles.

Although photochemical air pollutants are believed to be associated with respiratory illness, there is also a need to consider their possible effects on postnatal lung maturation. The purpose of this study was to determine whether the maturation of lungs of young beagle dogs might be altered by an inhalation exposure to ozone that represents a severe 5-d episode of photochemical oxidant air pollution. Exposures were at 6 wk of age to purified air, 1 or 2 ppm ozone for 4 h/d on 5 consecutive days. After holding for 6 wk in clean air, lungs were removed and weighed, and the left lung was fixed both by inflation at 30 cm pressure and immersion using buffered formalin. Histologic sections were used for morphometric measurements. Statistical analysis showed that the mean linear intercept (inversely related to lung surface area) was greater than controls (up to about 5%) in the 1 ppm ozone-exposed group. This effect was not seen at 2 ppm ozone, apparently due to large variations in mean linear intercept. No significant differences were seen in body weight, chest girth, lung weight, or volumes of the fixed, inflated lungs. It is concluded that if anatomic maturation of the lung was retarded by this brief regimen of ozone exposure, the effect was small and not likely to have major health consequences.

Animals↗

Bayesian analysis of a multivariate null intercept errors-in-variables regression model.

Longitudinal data are of great interest in analysis of clinical trials. In many practical situations the covariate can not be measured precisely and a natural alternative model is the errors-in-variables regression models. In this paper we study a null intercept errors-in-variables regression model with a structure of dependency between the response variables within the same group. We apply the model to real data presented in Hadgu and Koch (Hadgu, A., Koch, G. (1999). Application of generalized estimating equations to a dental randomized clinical trial. J. Biopharmaceutical Statistics 9(1):161-178). In that study volunteers with preexisting dental plaque were randomized to two experimental mouth rinses (A and B) or a control mouth rinse with double blinding. The dental plaque index was measured for each subject in the beginning of the study and at two follow-up times, which leads to the presence of an interclass correlation. We propose the use of a Bayesian approach to model a multivariate null intercept errors-in-variables regression model to the longitudinal data. The proposed Bayesian approach accommodates the correlated measurements and incorporates the restriction that the slopes must lie in the (0, 1) interval. A Gibbs sampler is used to perform the computations.

Bayes Theorem↗