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Belladonna alkaloids-induced behavioral changes and amnesia on open-field and step-through in 18-, 28-, and 38-day-old mice.

AIM: To study the age-related changes of atropine (Atr), scopolamine (Sco), anisodine (AT3), and anisodamine (Ani) on behaviors and memories. METHODS: The behaviors and memories were measured with open-field test and step-through task. M-cholinergic receptors were determined by [3H] quinuclidinyl benzilate ([3H] QNB). RESULTS: During acquisition session (d 1) the 18-, 28-, and 38-d-old mice pretreated with Atr, Sco, and AT3 (0.02, 0.2, 2, or 20 mg.kg-1, i.p.) in open-field test showed increase in walking counts by 26%-42%, but decrease in rearing, grooming, and defecating counts for 50%-92%, 67%-100%, and 75%-100%, respectively. On recall session (d 2) the walking and rearing behaviors in the 18- and 28-d-old mice receiving Atr, Sco, and AT3 on d 1 were higher than those in the mice receiving saline. But a lower grooming behavior on d 2 was found in the mice receiving the drugs on d 1. On d 1 Ani 20 mg.kg-1 reduced the rearing behavior by 50% in 18-d-old mice and defecation by 33%-36% in 18- and 28-d-old mice. All the 4 belladonna alkaloids increased the number of avoidance-response errors and decreased the retention latencies in step-through task. Bmax of [3H] QNB binding sites in frontal cortex and hippocampus regions in the 38-d-old mice increased 7% and 23% vs in the mice of 18 d of age, respectively. CONCLUSION: 1) The effects of the belladonna alkaloids on behaviors and memories in adult mice were weaker than those in young mice. 2) The belladonna alkaloids-induced amnesia on passive avoidance-response in step-through was more sensitive than behavioral changes and amnesia on open-field. 3) According to the lowest effective doses which insulted the behaviors or memories in young mice, Sco was about 10, 100, and 1000 times more potent than Atr, AT3, and Ani, respectively.

Age Factors↗

Non-invasive blood glucose measurement by Fourier transform infrared spectroscopic analysis through the mucous membrane of the lip: application of a chalcogenide optical fiber system.

Non-invasive blood glucose measurement through the mucous membrane of the lip was investigated using Fourier transform infrared (FT-IR) spectroscopy with an attenuated total reflection (ATR) prism. To achieve easy attachment and easy control of attachment pressure of the ATR prism to the mucous membrane of the lip, a chalcogenide optical fiber with an ATR prism built in the tip was used. The same glucose-specific peaks at wave numbers of 1080 and 1033 cm-1 as glucose solutions were found in a spectrum through the mucous membrane of the lip. With a constant pressure of the ATR prism to the mucous membrane of the lip of 6.7 x 10(3) dyn/cm2, coefficients of variation of measurements within the day and of day-to-day measurements were 3.8 and 5.4% respectively. To eliminate baseline drifts and interference of body constituents other than glucose, the difference absorbances at 1080 cm-1 between spectra measured at the postprandial state and background spectrum obtained at the fasting state as an individual characteristic were evaluated. Following i.v. pulsatile injection of glucose, the difference absorbances at 1080 cm-1 nicely followed the changes in blood glucose concentrations with a time delay of 4 min. In daily blood glucose monitoring, a highly significant correlation between the difference absorbances and increases in blood glucose concentrations above the fasting level was obtained (r = 0.920, P < 0.01). From these experiments, it was suggested that FT-IR spectroscopy with a chalcogenide optical fiber could be useful clinically for non-invasive monitoring of glucose through the mucous membrane of the lip.

Adult↗

[Sensitivity and adaptation of various Brucella species to acid shock].

The sensitivity to acid shock (pH 2.5, 2.8, 3.0, and 3.3) and the capacity to adaptive acid tolerance response (ATR) is studied in the reference Brucella strains differing by the origin, biological, and virulent properties. The ability of Brucella to survive under conditions of acid pH depended on the medium composition, growth phase, and preliminary adaptation at pH 5.6. B. suis biovar 1 and B. melitensis biovar 3 were more resistant to low pH than other Brucella species. Adaptation by overnight growth at pH 5.6 (stationary phase) induced ATR to the acid shock (pH 3.3-3.0) in all Brucella species except B. abortus biovar 1. ATR induced in B. melitensis biovar 2, B. canis, and B. neotomae was more marked, with more than an 100-fold increase in survival of adapted cultures, while adapted B. suis biovar 1, B. melitensis biovars 1 and 2 showed a 2-24-fold increase in survival rates. The detected differences in acid sensitivity and ATR of various Brucella species may be useful for identification and characterization of Brucella strains.

Adaptation, Physiological↗

Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following deoxyribonucleic acid damage.

The breast/ovarian cancer susceptibility gene BRCA1 exerts its tumor suppressor function, at least in part, by participating in DNA repair and/or DNA damage-responsive pathways. BRCA1 protein is hyperphosphorylated following various DNA-damaging events. Here, we report that the ataxia telangiectasia mutated protein-related protein kinase (ATR) is involved in the phosphorylation of BRCA1 following gamma radiation and hydroxyurea treatment. We have shown that ATR can phosphorylate several BRCA1 fragments in vitro and that a kinase-inactive mutant of ATR interacts with BRCA1 in vivo. Taken together, these results suggest that ATR directly phosphorylates BRCA1 following DNA damage.

Androstadienes↗

The infrared spectroscopic Gram stain.

The attenuated total reflectance (ATR) spectra of bacterial colonies were obtained in situ, without their removal from the agar growth media using the infrared microscope. Principal components regression (PCR) analysis was used to obtain a measure of the differentiating potential of the ATR spectra obtained on two standard sets consisting of 31 and 44 species, respectively, grown on trypticase soy agar. A quantitative response value of +1 was assigned to Gram positive species and -1 was assigned to Gram negative species. In a cross validation experiment, the Gram stain property correlated with the factor loadings with a multiple correlation of 0.9502 and 0.9520 for each of the standard sets, respectively. Also, it was found that ATR spectra can be obtained from bacteria grown on blood agar and still have good differentiating capabilities for Gram stain. In addition, ATR spectra provide significantly better differentiating spectral information and predicting capabilities than specular reflectance spectra obtained in situ. Finally, the numerical value obtained for the Gram stain can be used as a measure of Gram variability. Results indicate that the Gram positive values shift to Gram negative values as the bacterial cell wall deteriorates with time.

Bacteriological Techniques↗

[Characteristics of hemodynamics and metabolism and structural polymorphisms of angiotensin converting enzyme and angiotensin II type I receptors genes in women of childbearing].

Parameters of systemic and intracardiac hemodynamics, characteristics of metabolism, and structural polymorphisms of angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (ATR(1)) genes were studied in women of childbearing age and men of the same age both with first degree hypertension. Women had lower mean 24-hour blood pressure (BP), greater BP variability, preponderance of "dipper" variant of 24-hour systolic and diastolic BP profile, higher prevalence of left ventricular hypertrophy, lower blood levels of cholesterol, triglycerides, urea and potassium. Among women A allele of ATR(1) gene was significantly more frequent than C allele. Comparison of ATR(1) gene polymorphisms in women and men showed that frequencies of AA genotype and A allele were higher in women. Presence of DD genotype of ACE gene in women was related to parameters of both hemodynamics and metabolism, whereas that of II genotype of ACE gene as well as AA and AC genotypes of ATR(1) gene were linked with parameters of hemodynamics.

Adult↗

Overview of infrared methodologies for trans fat determination.

trans Fatty acids are present in a variety of foods like dairy products, but the major sources are products that contain commercially hydrogenated fats. Some studies have shown that trans fatty acids elevate levels of serum low-density lipoprotein (LDL)-cholesterol and lower high-density lipoprotein (HDL)-cholesterol. The quantitation and identification of trans fatty acid isomers is difficult because of the wide range of positional monoene, diene, and triene fatty acid isomers present in hydrogenated oils. This is complicated by the cis positional isomers that are also present, as well as the lack of commercial chromatographic standards for many fatty acid isomers. In this review, infrared methodologies for the determination of total trans fat are presented. Using an attenuated total reflection (ATR) infrared cell, a novel Fourier transform infrared (FTIR) spectroscopic method that was developed for the rapid (5 min) quantitation of the total trans fatty acid levels in neat (without solvent) fats and oils measured as triacylglycerols (TAG) is discussed. TAG required no derivatization, but had to be melted prior to measurement. The lower limit of trans quantitation was 5% of total fat. The precision of this ATR method was found to be superior to that of transmission infrared official methods. Accuracy was enhanced by generating a symmetric absorption trans infrared band at 966 cm(-1) on a horizontal background. This was achieved by "ratioing" the single-beam spectrum of the trans-containing fat or oil against that of a reference oil or standard having only cis double bonds. Attempts to apply this ATR-FTIR method to food matrixes with low trans fat and/or low total fat content were not satisfactory due to interfering infrared absorptions in the trans region. To overcome this interference, the method was modified by applying the standard addition technique to the ATR-FTIR determination. The modified procedure required more time, but eliminated any adverse impact on accuracy arising from interfering minor food components having absorption bands near 966 cm(-1).

Spectroscopy, Fourier Transform Infrared↗

Chromatin association of rad17 is required for an ataxia telangiectasia and rad-related kinase-mediated S-phase checkpoint in response to low-dose ultraviolet radiation.

Activation of the S-phase checkpoint results in an inhibition of DNA synthesis in response to DNA damage. This is an active cellular response that may enhance cell survival and limit heritable genetic abnormalities. While much attention has been paid to elucidating signal transduction pathways regulating the ionizing radiation-induced S-phase checkpoint, less is known about whether UV radiation initiates the process and the mechanism controlling it. Here, we demonstrate that low-dose UV radiation activates an S-phase checkpoint that requires the ataxia telangiectasia and Rad-related kinase (ATR). ATR regulates the S-phase checkpoint through phosphorylation of the downstream target structural maintenance of chromosomal protein 1. Furthermore, the ATPase activity of Rad17 is crucial for its chromatin association and for the functional effects of ATR activation in response to low-dose UV radiation. These results suggest that low-dose UV radiation activates an S-phase checkpoint requiring ATR-mediated signal transduction pathway.

Adenosine Triphosphatases↗

Structural studies of trimethoxysilane containing R'R"Im+I- ionic liquid and its nanocomposite with tetramethoxysilane (TMOS).

A dialkylsubstituted imidazolium iodide ionic liquid (1-methyl-3-[3-(trimethoxy-lambda4-silyl)propyl]imida-zolium iodide, MTMSPIm+I-) was prepared with the intention of using it as a quasi-solid-state electrolyte for dye-sensitized photoelectrochemical (DSPEC) cells of Grätzel design, while the analogous electrolyte in a gel state was made by the addition of tetramethoxysilane (TMOS) in the molar ratio MTMSPIm+I-:TMOS = 1:1. The structure of the MTMSPIm+I- in its non-hydrolyzed and hydrolyzed states and in its fully condensed form, obtained after ageing the sols for various times (from a few hours to a few weeks) and heating them at 200 degrees C (fully condensed form), was studied employing time-dependent infrared attenuated total reflection (ATR) and 29Si NMR spectroscopic measurements. The structure of the condensed species was correlated with the viscosity and the specific conductivity measurements of MTMSPIm+I- sols and TMOS/MTMSPIm+I- gels during their ageing. The final product of the condensation of MTMSPIm+I- sols was described as a positively-charged ladder-like polysilsesquioxane with Tn end groups exhibiting a single T3 signal in 29Si NMR spectra and characteristic doublet bands at 1138 and 1049 cm(-1) in IR. This structure was retained to a large extent in TMOS/MTMSPIm+I- gels, confirming their nanocomposite structure. The results of the ATR infrared time-dependent spectroscopic studies showed that in the course of condensation of sols, the refractive index of the modes attributed to the polysilsesquioxane species exhibited strong dispersion, which led to shifts in the vibrational band positions in the experimental ATR spectra. This effect accompanies the sol-to-gel transformations and has not yet been considered as a possible error in analysis of the ATR spectra of sols and gels. The calculation procedure for obtaining the corresponding transmission spectra is briefly outlined and the results applied in this work.

Molecular Structure↗

Topical anesthetics: effects on the Achilles tendon and H-reflexes. I. Able-bodied subjects.

Achilles tendon reflexes (ATR) and H-reflexes were monitored to determine changes in motor responses after the application of a benzocaine spray or an air spray to normal individuals. There was no change in ATR after application of the spray or the benzocaine, even when the sequence of reflex elicitation was reversed. The only significant change (p less than 0.05) in the H-reflex was an increase in its amplitude from baseline at all posttest times following (1) the placebo application when the H-reflex preceded the ATR (0.264 +/- 0.054V, ten minutes; 0.290 +/- 0.054V, 20 minutes; and 0.322 +/- 0.058V, 30 minutes), and (2) the benzocaine spray when the ATR preceded the H-reflex (0.277 +/- 0.084V, ten minutes; 0.309 +/- 0.152V, 20 minutes; and 0.329 +/- 0.131V, 30 minutes). Within-group comparisons revealed that a significantly greater H-reflex (p less than 0.05) was obtained at 20 and 30 minutes after air spray when H-reflex/ATR test sequence was used, whereas at 30 minutes after application of the benzocaine spray a significantly greater H-reflex was seen using the ATR/H-reflex test sequence. Changes in H-reflex amplitude appear to be as much a function of the reflex testing sequence as whether an air or benzocaine spray is used.

Achilles Tendon↗

Neuromuscular blocking drug pharmacodynamics after chronic exposure to H2- antagonists.

This study tested the hypothesis that chronic exposure to H2-antagonists may affect neuromuscular function. Cimetidine or ranitidine was administered to rats for twenty one days as subcutaneously implanted biodegradable pellets. Control rats received placebo pellets. Serum cimetidine and ranitidine concentrations ranged from 0.1 to 0.5 micrograms/mL over this period. On the study day, surgically prepared anaesthetized rats received either succinylcholine (SCh) or atracurium (ATr) to achieve complete paralysis of the tibialis anterior muscle. After recovery an infusion dose of each neuromuscular blocker was titrated to produce 50% muscle paralysis with each blocker. Exposure to cimetidine or ranitidine did not alter SCh or ATr dose to maximum paralysis or the time course of recovery from the initial paralysis. SCh or ATr infusion rates required to elicit 50% paralysis were also unaffected by cimetidine or ranitidine pretreatment. These results indicate that chronic exposure to cimetidine or ranitidine at human therapeutic concentrations does not affect the neuromuscular pharmacodynamics of SCh or ATr in rats.

Animals↗

[The effect of different antitubercular agents on phagosome fusion with lysosomes, on the F-actin content in mouse peritoneal macrophages and on G-actin polymerization in vitro].

Effects of various antituberculosis remedies (ATR)--isoniazid (INA), saluzid (SA), streptosaluzid (SS), ethambutol (EB), sodium para-aminosalicylate (SPAS) on phagosome-lysosome (PL) fusion, on F-actin content in mouse macrophages and on G-actin polymerization in vitro were studied. The ATR of choice have been shown to stimulate the PL fusion. INA (0.2 mM), SA (0.02 mM), SS (0.05 mM), EB (0.08 mM) and SPAS (0.5 mM) increased the F-actin content and changed its localization within macrophages. ATR changed the character of G-actin polymerization in vitro. Possible mechanisms of interrelation between cytoskeleton (actin part) changes and PL fusion are discussed. The results obtained suggest to use the ATR-induced changes in PL fusion and F-actin content in the cells for estimating therapeutic effects of respective antituberculosis remedies.

Actins↗

Quantitation of tendon reflexes in normal volunteers.

Ankle (ATR), patellar (PTR) and triceps (TTR) T-reflex responses were recorded in 48 limbs of 24 normal volunteers by delivering tendon taps with a hand operated electronic hammer. Latency to the onset of the triggered response, peak to peak amplitude and duration of the wave were measured after several repetitions. In all individuals, ATR and PTR were observed, while in 27% of limbs, TTR was absent. Shortest latency and duration of the elicited response were chosen to calculate normal means. Side differences were also evaluated. As amplitude showed a marked interindividual and side to side variation, lowest recorded value was selected to represent the lower limit of normal. Age, height, and leg length showed a good correlation with minimum ATR latency (p < 0.001). PTR latency correlated significantly with age, height, (p < 0.001) and thigh length (p < 0.001). No significant correlation existed between age, height, arm length and TTR latency (p > 0.01). In conclusion, ATR and PTR are acceptable tests in clinical practice, whereas TTR is not reliable, as it is technically difficult to elicit in some normal individuals.

Adult↗

Surveillance for nonfatal work-related injuries in Alaska, 1991-1995.

Historically, Alaska has had an occupational fatality rate five times greater than that for the United States. This article reports recent surveillance results for hospitalized nonfatal work-related injuries in Alaska, using the population-based Alaska Trauma Registry (ATR) from 1991 through 1995. The fishing, construction, and logging industries led with the highest number of reported cases in the ATR. Workers in the logging, water transportation, and wood product manufacturing industries had the highest injury rates. Cause, severity, type, and body region of injury were examined for each target industry. For industries with the highest numbers and rates of injuries, in most cases, falls were identified as a common cause of injuries. A fractured bone was the most common type of injury, and the extremities were the most common body region affected. The ATR has proved to be a reliable tool for work-related injury surveillance and will be helpful in planning research priorities and targeting injury prevention efforts.

Accidental Falls↗

Synthetic scleral reinforcement materials. III. Changes in surface and bulk physical properties.

Changes in the physical properties of polymer materials during implantation in the biological environment can directly affect the ultimate performance of the polymer and/or device. We implanted four types of extraocular bands (porous, solid, composite, and patched) made from 11 types of materials in rabbit eyes and examined the changes in the physical strength and polymer structure of the implanted bands in terms of tensile strength measurements, creep analysis, and attenuated total internal reflectance--Fourier transform infrared spectroscopy (ATR-FTIR) at intervals up to 18 months after implantation. Most of the materials showed increases in tensile strength over the first 6 months in situ in the rabbit eye, followed by significant decreases between 6 and 18 months. Polymer bands that had been implanted for 18 months generally exhibited less creep behavior than unimplanted controls; for most of the bands, creep values ranged from 0% to 10% of the original length. ATR-FTIR of the solid bands and surface coatings showed protein deposition on all of the materials examined, with silicone materials and coatings least affected. Thirty-degree ATR-FTIR scans detected significant changes in the polymer structure for two of the band types: one solid (polyether urethane) and one porous (porous polyacrylate). In general, expanded polytetrafluoroethylene was the most stable in terms of tensile strength and creep. The least stable bands (composite bands made with porous polyurethane) were those that had undergone hydrolytic and/or oxidative degradation and chain scission of the polymer or alteration of the bond between the two materials making up the composite. These changes in physical properties and polymer structure observed after 18 months of implantation support the idea that polymer implant materials should be followed closely over several years in vivo to determine their suitability prior to use in humans.

Animals↗

Attenuated total reflection IR spectroscopy as a tool to investigate the structure, orientation and tertiary structure changes in peptides and membrane proteins.

During the last few years, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) has become one of the most powerful methods to determine the structure of biological materials and in particular of components of biological membranes, like proteins that cannot be studied by x-ray crystallography and NMR. ATR-FTIR requires a little amount of material (1-100 microg) and spectra are recorded in a matter of minutes. The environment of the molecules can be modulated so that their conformation can be studied as a function of temperature, pressure, pH, as well as in the presence of specific ligands. For instance, replacement of amide hydrogen by deuterium is extremely sensitive to environmental changes and the kinetics of exchange can be used to detect tertiary conformational changes in the protein structure. Moreover, in addition to the conformational parameters that can be deduced from the shape of the infrared spectra, the orientation of various parts of the molecule can be estimated with polarized IR. This allows more precise analysis of the general architecture of the membrane molecules within the biological membranes. The present review focuses on ATR-IR as an experimental approach of special interest for the study of the structure, orientation, and tertiary structure changes in peptides and membrane proteins.

Animals↗

Vascular graft healing. II. FTIR analysis of polyester graft samples from implanted bi-grafts.

FTIR-ATR analysis has shown that the 4-step process for preclotting polyester vascular grafts results in a uniform and reproducible fibrin coating of the polyester fibers. Western blot analyses have shown that FN and VEGF are also present in this fibrin coating. FTIR-ATR analyses of explanted grafts indicate that, while the in vivo healing of these preclotted polyester grafts proceed through the inflammation, proliferation, and remodeling phases of normal wound healing, these phases are modified. Because the fibrin coating provides a nonporous barrier between peri-graft tissue and the flowing blood, these molecular changes are controlled by the interactions of blood-borne constituents with the lumenal surface of the preclotted graft. Also, a well prepared preclotted polyester graft shows a minimal inflammatory response. After implantation, the fibrin preclot is more than 90% gone by the fifth day. However, the proliferation phase, involving synthesis of new protein and polysaccharide materials to replace the fibrin, appears to have begun by the third day. Detection of collagen I in the 5-day explants suggests that the overlapping remodeling phase of healing has begun. Protein and saccharide materials continue to be synthesized and remodeled, and, by the tenth day, collagen IV is detected. By 14-days post-implantation, there is an increase in collagen IV and cellular membrane lipids. Because collagen IV is an indicator of the presence of endothelial cells, some of these cellular membranes must be of endothelial origin. Thus, it appears that FTIR-ATR can be a useful tool in the study of vascular healing.

Animals↗

Permeation enhancement of a highly lipophilic drug using supersaturated systems.

The potential of supersaturation as a method for enhancing the membrane permeation of highly lipophilic compounds has been investigated using, as a model system, the transport of a lavendustin derivative (LAP, log K(o/w) = 5) through silicone membrane. Propylene glycol-water mixtures, which permitted the formulation of LAP at different levels of saturation, were prepared and tested for stability prior to conducting membrane permeation studies. The transport of LAP across silicone membrane from donor solutions containing the drug at different degrees of saturation (DS = 1-5) was evaluated by two independent experimental methods: (i) using attenuated total-reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and (ii) using standard vertical diffusion cells followed by quantification with high-performance liquid chromatography (HPLC). Both methods demonstrated a linear relationship between the DS of the applied solution and the flux through the membrane, yielding similar values for the diffusion coefficients of LAP [diffusion cells, D = 1.75 ( +/- 0.16) x 10(-7) cm(2) s(-1) and ATR-FTIR, D = 1.42 ( +/- 0.26) x 10(-7) cm(2) s(-1)). In addition to the characterization of LAP permeation, ATR-FTIR spectroscopy enabled an examination of solvent transport across the membrane.

Diffusion Chambers, Culture↗