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Intrinsic fat suppression in TIDE balanced steady-state free precession imaging.

A novel fat-suppressed balanced steady-state free precession (b-SSFP) imaging method based on the transition into driven equilibrium (TIDE) sequence with variable flip angles is presented. The new method, called fat-saturated (FS)-TIDE, exploits the special behavior of TIDE signals from off-resonance spins during the flip angle ramp. As shown by simulations and experimental data, the TIDE signal evolution for off-resonant isochromats during the transition from turbo spin-echo (TSE)-like behavior to the true fast imaging with steady precession (TrueFISP) mode undergoes a zero crossing. The resulting signal notch for off-resonant spins is then used for fat suppression. The efficiency of FS-TIDE is demonstrated in phantoms and healthy volunteers on a 1.5T system. The resulting images are compared with standard TrueFISP data with and without fat suppression. It is demonstrated that FS-TIDE provides a fast and stable means for homogenous fat suppression in abdominal imaging while maintaining balanced SSFP-like image contrast and signal-to-noise ratio (SNR). The scan time of FS-TIDE is not increased compared to normal TrueFISP imaging without fat suppression and identical k-space trajectories. Because of the intrinsic fat suppression, no additional preparation is needed. Possible repetition times (TRs) are not firmly limited to special values and are nearly arbitrary.

Adipose Tissue↗

Genetic and molecular basis for cellular senescence.

Normal human and rodent cells in culture exhibit a finite life span at the end of which they exhibit morphological changes and cease proliferating, a process termed cellular senescence or cellular aging. Many cancer cells differ from normal cells in that they do not senesce and have an indefinite life span in culture, suggesting that alterations relating to cellular senescence are involved in the neoplastic evolution of tumor cells. Recent experimental results strongly support a genetic basis for cellular senescence. Defects in the senescence program in transformed cells can be corrected by introduction of a specific chromosome from normal cells into the abnormal cells. Using this approach, possible senescence genes have been mapped to specific chromosomes. Cell cycle control genes that regulate entry into the DNA synthetic phase of the cell cycle must be altered in senescent cells. Recent findings suggest that phosphorylation of the retinoblastoma gene is altered in senescent cells. It is possible, but not yet proven, that aging at the cellular level contributes to the aging of the individual. Therefore, an understanding of cellular senescence at the genetic and molecular levels may provide new insights into both the cancer and aging processes.

Animals↗

Evolution of energy failure after repeated cerebral ischemia in gerbils.

We have examined the regional differences in the evolution of energy failure in experimental focal cerebral ischemia. In gerbil brain subjected to repeated unilateral common carotid artery occlusion, the tissue ATP content, pH and succinic dehydrogenase activity decreased at different rates after the circulation had been restored in various cerebral regions. Light microscopical infarction became apparent at different rates following the impairment of the energy metabolism in these regions. In brain cortex with selective neuronal necrosis, only minor alterations in energy metabolism were detectable over a 7-day period following the restoration of the circulation. The present data show that the rate of energy failure is significantly different in various cerebral regions after repeated periods of cerebral ischemia in the gerbil. A slowly evolving impairment of the cerebral energy metabolism after circulation of the brain has been restored appears to be indispensable for the delayed formation of infarction after transient cerebral ischemia.

Acid-Base Equilibrium↗

Population density effects on longevity.

Population density, or the number of adults in an environment relative to the limiting resources, may have important long and short term consequences for the longevity of organisms. In this paper we summarize the way in which crowding may have an immediate impact on longevity, either through the phenomenon known as dietary restriction or through alterations in the quality of the environment brought on by the presence of large numbers of individuals. We also consider the possible long term consequences of population density on longevity by the process of natural selection. There has been much theoretical speculation about the possible impact of population density on the evolution of longevity but little experimental evidence has been gathered to test these ideas. We discuss some of the theory and empirical evidence that exists and show that population density is an important factor in determining both the immediate chances of survival and the course of natural selection.

Animals↗

Evolution of brain abscess in cats formation of capsule and resolution of brain edema.

Brain abscess evolution was studied in an experimental model in the cat correlating the computed tomographic scan appearance with intracranial pressure, brain edema and histopathological findings. Brain inflammation was produced by direct inoculation of Staphylococcus aureus into the white matter. Abscesses developed in all animals. The ring enhancement around the necrotic focus seen at an early stage after contrast-medium injection cannot be equated with capsule formation as long as the abscess diameter increased. Parallel to the acute stage of abscess, the intraventricular pressure increased due to the rising mass effect and the spreading edma. The morphological investigations revealed on the seventh day an extreme enlargement of extracellular spaces with immense amount of edema fluid, rich in protein and fibrin. Some blood vessels in the close vicinity of the abscess showed gaps within the endothelial cell layer. When encapsulation developed, ring enhancement became more homogeneous and decreased in diameter. In spite of encapsulation, a circumscribed disturbance of the blood-brain barrier persisted which was responsible for a belated resolution of edema and a slow decrease of intracranial pressure. Only therapy with dexamethasone could effect a marked change in the course of the disease.

Animals↗

Postoperative evolution of inflammatory response in a model of suprarenal aortic cross-clamping with and without hemorrhagic shock. Systemic and local reactions.

Surgery of the abdominal aorta generates a systemic inflammatory response (SIR), a source of operative morbidity-mortality. In the present work we attempted to evaluate the evolution of SIR in an experimental model that simulates elective and urgent surgery on the abdominal aorta. Fifteen mini-pigs divided into three groups were used. The animals were subjected to suprarenal aortic/iliac clamping and bypass with a Dacron-collagen prosthetic graft. Groups were as follows: (1) sham (only aortic dissection); (2) clamping and bypass; (3) hemorrhage of 40%, pre-clamping, and bypass. Determinations included (1) tumor necrosis factor-alpha (TNF-alpha) interleukin (IL)-1beta, IL-6, IL-10, interferon-gamma; (2) myeloperoxidase (MPO), superoxide anion (SOA), superoxide dismutase (SOD), and malondialdehyde (MDA); (3) nitrites; (4) iNOS, (5) cell adhesion molecules (ICAM-1, VCAM-1) at 24 hours, 48 hours, and on day 7; and (6) NFkappaB at 48 hours. Our results point to an increase in all inflammatory variables, corroborated by their molecular regulators such as the expression of CAMs, iNOS, and NFkappaB. The alterations tended to normalize by day 7, after reperfusion. The results point to the great importance of SIR at all levels (molecular, nuclear, cellular, and systemic) in situations such as elective and urgent abdominal aorta surgery and the role that control of this response could represent for the future of vascular surgery.

Animals↗

Mathematical modeling of fracture healing in mice: comparison between experimental data and numerical simulation results.

The combined use of experimental and mathematical models can lead to a better understanding of fracture healing. In this study, a mathematical model, which was originally established by Bailón-Plaza and van der Meulen (J Theor Biol 212:191-209, 2001), was applied to an experimental model of a semi-stabilized murine tibial fracture. The mathematical model was implemented in a custom finite volumes code, specialized in dealing with the model's requirements of mass conservation and non-negativity of the variables. A qualitative agreement between the experimentally measured and numerically simulated evolution in the cartilage and bone content was observed. Additionally, an extensive parametric study was conducted to assess the influence of the model parameters on the simulation outcome. Finally, a case of pathological fracture healing and its treatment by administration of growth factors was modeled to demonstrate the potential therapeutic value of this mathematical model.

Animals↗

Effects of acute tilt from orthostatic to head-down antiorthostatic restraint and of sustained restraint on the intra-cerebroventricular pressure in rats.

The tail-cast suspension rat model was developed to explore in ground laboratories the physiological effects of some of the stresses prevailing during space flight including and among them those of the headwards body fluid shifts. We recently showed in rats that an acute head-down tilt (45 degrees) from tail-cast orthostatic (OR) to antiorthostatic restraint (AOR) induced within 30 min and for 2 to 4 h an acute stress-like surge in plasma ACTH and corticosterone levels. Considering the proximity of the CRF producing neurons with the 3rd ventricle, we decided to explore the acute and longer-term effects of the OR/AOR tilt on the intra-cerebroventricular pressure (Picv) measured with an indwelling sensor-transmitter catheter stereotaxically implanted in the 3rd ventricle. At 1- or 10-min intervals the unit sent radiotelemetric signals for both Picv and motor activity (MA) to a receiver coupled with an automatic data analyser. The acute AOR-tilt induced within 10 min and for 60 min a 2.5-fold rise in Picv which receded to baseline between 60 and 90 min. During this time, the normally close correlation between Picv and MA was lost, as assessed by Spearman's rank coefficient. In a long-term experimental series we explored the evolution of both Picv and MA in individual rats subjected successively to a 7 day control phase (C). 7 days OR, and 3 days AOR. After the 1-h-long post-tilt rise of the Picv, the mean Picv levels measured for the next 3 days decreased significantly vs. both the preceding OR phase (-30%) and the initial C Phase (-40%). The circadian pattern of the diurnal Picv profile was impaired, as evidenced by a significant fall (i) in the night/day ratio (-25% vs. C). and (ii) even more in the spectral power of the circadian 1 c/24 h frequency (-85% vs. C). The simultaneously recorded MA fluctuations similarly displayed an altered diurnal pattern with a spectral power of the circadian frequency reduced to 7% of controls. However, contrary to the short-term experiment, in the long-term study the large alterations to both Picv and MA were strongly correlated, as during the control phase. The mechanisms involved in the swift post-tilt rise in the Picv together with an aroused corticotropic axis, and in the impact of sustained head-down restraint on CNS-controlled adaptive regulations including their circadian rhythms remain unknown.

Animals↗

Contingent negative variation and accuracy of time estimation: a study on cats.

Slow cortical potential shifts, similar to the contingent negative variation (CNV) discovered in man, were analysed in cats submitted to a schedule of temporal conditioning. Two situations were compared, according to information delivered during a 7 sec delay: in the first (A), a fixed visual signal appeared on an oscilloscope screen; in the second (B), the signal moved across with time. In both cases, the cat had to press a lever 5-7 sec after signal onset. The CNV recorded during the delay had different amplitudes according to the cortical site involved. It could be dissociated into two components, which showed similar evolutions as a function of experimental conditions. The characteristics of the CNV as a whole varied with temporal parameters. CNV amplitude and time course were related to the accuracy of the cat's responses; prolonged training in unchanged experimental conditions led to a decline in negativity, which seemed to reflect automation of time estimation processes. These data suggest that CNV may be an index of a phase of information processing aimed at constituting internal time bases congruent with a particular situation.

Animals↗

Dielectric analysis and Differential Scanning Calorimetry of water-in-oil microemulsions.

The system investigated is a multicomponent thermodynamically stable liquid consisting of water spherical droplets, (approximately 10 nm diameter), stabilized by a surfactant shell and dispersed in a continuous oil phase (microemulsions). A comparative analysis is carried out among the results obtained with three different experimental approaches, namely, dielectric analysis, Thermally Stimulated Depolarization, and Differential Scanning Calorimetry. The different measurement procedures are briefly described. The attention was focused on the system water concentration. Two microemulsions, differing only in the oil used as continuous phase, were studied. For any concentration a comparison between the results obtained with the different experimental methods was undertaken. The evolution with water addition of the water/oil interphase region was analysed in some detail.

Journal Article↗

Portal hypertension produces an evolutive hepato-intestinal pro- and anti-inflammatory response in the rat.

An inflammatory etiopathogeny can be suggested in portal hypertensive enteropathy since infiltration of the intestinal wall by mononuclear cells has been described in this condition. This work was carried out with the intention of shedding light on this matter. Male Wistar rats were divided into 4 control groups and 4 groups with partial portal vein ligation at 1, 2, 3 and 15 months. TNF-alpha, IL-1beta and IL-10 were quantified in liver and ileum by ELISA. CO and NO were measured in splanchnic and systemic vein by spectrophotometry and Griess reaction, respectively. Expression of constitutive and inducible isoforms of NO and HO were assayed by Western blot in liver and ileum. An increased hepatic release of proinflammatory mediators (TNF-alpha, IL-1beta and NO) associated with intestinal release of anti-inflammatory mediators (IL-10, CO) occurs in an early evolutive phase (1 month) of experimental portal hypertension. On the contrary, in the long-term (15 months), the increase in the intestinal release of proinflammatory mediators (TNF-alpha, IL-1beta) is associated with an increase in the hepatic release of anti-inflammatory mediators (IL-10, CO). These results suggest that experimental prehepatic portal hypertension presents changes in the serum and tissular (liver and small bowel) concentrations of mediators which are considered as pro- and anti-inflammatory.

Animals↗

Tolerogenic protocols for intestinal transplantation.

The intestine has long been considered as a "forbidden" organ to transplant [Ann. Surg. 216 (1992) 223-33]. This is due to the particularly challenging nature of the immunological conflict that an intestinal graft may cause: a particularly vigorous rejection response, in addition to the capacity to mount a graft-versus-host disease (GVHD) [Transplantation 37 (1984) 429]. Currently, the short-term success of intestinal transplantation (Itx) depends upon the chronic delivery of profound immunosuppression but this causes infection, malignancies--in particular posttransplant lymphoproliferative disorder (PTLD)--and direct drug toxicity. For these reasons, the results of Itx remain inferior to those of other solid organ transplants in the middle and in the long term (Intestinal Transplant Registry: www.small-bowel-transplant.org). Improved results and wider application of Itx requires the development of protocols that would facilitate acceptance of the new intestine thereby allowing to reduce the need for immunosuppression with its attending complications. Relevant experimental data and the recent evolution in the clinical strategies used to promote acceptance of intestinal grafts are reviewed.

Animals↗

Early-stage endometriosis: adhesion and growth of human menstrual endometrium in nude mice.

OBJECTIVE: To evaluate the implantation of menstrual endometrium and the early stages of evolution of endometriotic lesions. DESIGN: Experimental prospective study. SETTING: An academic research environment. ANIMALS: Ten nude mice. INTERVENTION(S): A minilaparotomy was performed to place fresh human menstrual endometrial samples in the peritoneal cavity. Removal of the transplants was performed successively on days 1, 3, and 5 by laparotomy. MAIN OUTCOME MEASURE(S): Adhesion of endometrial fragments and early stages of endometrial lesions was morphologically and immunohistochemically studied. RESULT(S): As early as day 1, stromal cells were found to be attached to the mesothelium. A progressive reorganization of epithelial and stromal cells into endometrial glands was observed. On day 5, cystic endometriotic lesions were characterized by more extensive proliferative activity in glandular cells and a higher VEGF score in stromal cells than that observed in previously removed transplants. CONCLUSION(S): Menstrual human endometrium is able to implant on intact mesothelium and to reorganize itself into structured glands and stroma under the influence of unknown factors. We suggest that stromal and glandular cells have two distinct roles: stromal cells are involved in the attachment process and glandular cells in the growth of the endometriotic lesion.

Adult↗

Headspace solid-phase microextraction analysis of 3-alkyl-2-methoxypyrazines in wines.

A procedure to determine 3-alkyl-2-methoxypyrazines in wines is described. It is based on the headspace solid-phase microextraction (HS-SPME) technique after a clean-up of the sample by distillation (previously acidified to pH 0.5) to remove ethanol and other volatile compounds that can interfere in the SPME. Determination is performed by means of capillary gas chromatography using a nitrogen-phosphorus detector. The method allows quantification of 3-isobutyl-2-methoxypyrazine, 3-sec-butyl-2-methoxypyrazine and 3-isopropyl-2-methoxypyrazine at their natural concentration levels and below their sensory thresholds in Cabernet Sauvignon and Merlot wines. The method was successfully applied to experimental red wines and the evolution of their pyrazine contents during the winemaking process was monitored. Pyrazine content increased during the first maceration day but did not change significantly during alcoholic and malolactic fermentation. Final contents in wines were 12-27 ng/l of 3-isobutyl-2-methoxypyrazine and 5-10 ng/l of 3-sec-butyl-2-methoxypyrazine.

Chromatography, Gas↗

Some effects of aqueous silica on the corrosion of iron.

Silica is an important natural component of ground and surface waters, and is sometimes added as an inhibitor to control "red water" problems caused by corroding iron pipes. However, the effect of silicates on many aspects of iron corrosion has never been assessed. Experiments with water containing 0.5, 10, 25 or 50mg/L of SiO(2) demonstrated a significant interplay between aqueous silica and iron corrosion. During this 4-month experiment, higher levels of silica caused more iron release to the water and decreased the size of suspended iron particles. The process of iron corrosion also changed aqueous silica concentrations; silica was released into the water from the cast iron during corrosion and was removed from the water by incorporation into the scale layer. Silica also affected the type of scale that formed on the iron coupons. Scale at the lower silica concentrations was fairly uniform and easy to remove from the coupons, while the scale from the high silica reactors was more dense, and was more difficult to remove. Scale from the high concentration silica reactor also developed tall tubercles, and hydrogen gas-containing bubbles were channeled to solution through these tubercles. Iron corrosion occurring via the evolution was significant under all experimental conditions.

Corrosion↗

Integration of foreign DNA and its consequences in mammalian systems.

The insertion of foreign DNA into the genomes of established cells and organisms and the consequences of this integration event are of significance for viral oncology, reverse genetics, transgenic organisms, human somatic gene therapy and evolution. This review summarizes recent experimental findings and focuses on the alteration of cellular DNA methylation at regions remote from the site of insertion. We also discuss experimental data demonstrating that foreign DNA ingested by mice is not completely degraded in their gastrointestinal tracts; fragments of this DNA have been found to be covalently linked to DNA with 70% homology to the mouse IgE receptor gene.

Animals↗

Cryosurgical treatment of endolymphatic hydrops.

Cryosurgery of the labyrinth, as a treatment of endolymphatic hydrops, was initially greeted with considerable enthusiasm, but has lately received little publicity. That it still has a valuable role is demonstrated by this study of 69 patients who underwent labyrinthine cryosurgery over a 16 year period. Complete relief from vertigo has been achieved in 71 per cent of cases and morbidity has been minimized by the precautions outlined. The literature is reviewed to demonstrate the superiority of the transmastoid approach, the evolution of the technique and experimental evidence for the supposed mode of action.

Adolescent↗

A dynamic mathematical model to clarify signaling circuitry underlying programmed cell death control in Arabidopsis disease resistance.

Plant cells undergo programmed cell death in response to invading pathogens. This cell death limits the spread of the infection and triggers whole plant antimicrobial and immune responses. The signaling network connecting molecular recognition of pathogens to these responses is a prime target for manipulation in genetic engineering strategies designed to improve crop plant disease resistance. Moreover, as alterations to metabolism can be misinterpreted as pathogen infection, successful plant metabolic engineering will ultimately depend on controlling these signaling pathways to avoid inadvertent activation of cell death. Programmed cell death resulting from infection of Arabidopsis thaliana with Pseudomonas syringae bacterial pathogens was chosen as a model system. Signaling circuitry hypotheses in this model system were tested by construction of a differential-equations-based mathematical model. Model-based simulations of time evolution of signaling components matched experimental measurements of programmed cell death and associated signaling components obtained in a companion study. Simulation of systems-level consequences of mutations used in laboratory studies led to two major improvements in understanding of signaling circuitry: (1) Simulations supported experimental evidence that a negative feedback loop in salicylic acid biosynthesis postulated by others does not exist. (2) Simulations showed that a second negative regulatory circuit for which there was strong experimental support did not affect one of two pathways leading to programmed cell death. Simulations also generated testable predictions to guide future experiments. Additional testable hypotheses were generated by results of individually varying each model parameter over 2 orders of magnitude that predicted biologically important changes to system dynamics. These predictions will be tested in future laboratory studies designed to further elucidate the signaling network control structure.

Apoptosis↗