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PubMed1992

A graphics program for the analysis and display of molecular dynamics trajectories.

The program SCARECROW has been developed to help the molecular modeler to analyze and display the very big and complex data files produced by molecular dynamics programs. The molecular graphics program SCARECROW is written to support the display, animation, and extensive analysis of molecular dynamics trajectories. Using the macro language it is easy to make scripts for video animation and for the automated display and analysis of time series. Extensive coloring and atom selection commands are included to help the user to focus on relevant regions of the molecule. Time series can be produced and viewed on the screen or transferred to other programs.

Chemical Phenomena↗
PubMed1996

Studies of the interaction of gravity with biological membranes using alamethicin doped planar lipid bilayers as a model system.

Gravity interacts with biological systems on different levels of complexity. For the understanding of the action of gravity on such systems at higher degrees of organisation, the investigation of interactions on the membrane and even on the molecular level is crucial. To do such studies, planar lipid bilayers with incorporated transport mediating molecules, i.e. membranes of defined biochemical composition, are close to perfect model systems. In our experiments we have used painted planar lipid bilayers doped with alamethicin. Alamethicin is especially suitable for such studies because of its high sensitivity to applied external forces, which is a result of its special pore forming mechanism. Additional, different to most other transport mediating molecules, a big amount of data from the literature is available about the dependency of alamethicin pores on physical and chemical membrane parameters. We found that the conductance of alamethicin doped bilayers is dependent on the angle of the bilayer with the gravitational vector and that it furthermore can be reduced significantly under hyper gravity conditions in a centrifuge. The effect of gravity here is not an effect on the pore conductance or the membrane-aqueous solution interface, but it is due to an interaction of gravity with the pore forming mechanism, as can be shown by investigating the dependency of the alamethicin pore kinetics on the applied forces.

Alamethicin↗
PubMed2004

[Treatment in the primary prevention of stroke--still not fully used option].

Several studies have shown that pharmacological treatment of systolic-diastolic hypertension or isolated systolic hypertension in elderly persons would result in several years in a significant decrease (more than 40%) of stroke. Occurrence of strokes decreased in the Czech Republic in years 1985 till 2002 by more than 40%, which represents about two thirds of the decrease observed in the USA. Nevertheless, we cannot be satisfied with the treatment of hypertension in the Czech Republic because only 18% of patients are effectively treated for the hypertension, with BP < 140/90 mm Hg. Not well controlled hypertension results namely from the minimal use of the combination treatment. From the point of prognosis for the hypertensive patients older than 50 years, the level of systolic pressure is more important than the diastolic pressure. The risk of development of the stroke rises from the level of systolic blood pressure 115 mmHg almost linearly. Calcium channel blockers or diuretics represent the most appropriate therapy of the isolated systolic hypertension of elderly patients. The risk of stroke is higher also in persons with elevated blood pressure in the morning. That is why in elderly patients the use of drugs effectively controlling blood pressure during 24 hours is necessary. Recent studies (HOPE study, PROGRESS study) have demonstrated that the reduction of blood pressure decreases the occurrence of stroke not only in hypertensive patients, but also in the normotensive persons during the primary and secondary prevention. Review data show that 27% of ischemic strokes and 57% of hemorhagic strokes, which happened in the "treated" hypertensive patients, are due to not well controlled hypertension. Missing treatment of hypertension is responsible for 22.8% of strokes in men and 25.4% in women. The given data show a big reserve for the possibility to decrease further the stroke incidence in the population.

Antihypertensive Agents↗
PubMed1986

[Surgery of acoustic neurinoma in a hemodialyzed patient].

Successful surgical treatment of acoustic neurinoma in a case of hemodialyzed patient is reported. A 42-year-old female patient, who had been treated by hemodialysis, was diagnosed as having a C-P angle tumor by CT scan. She was refered to our clinic on June 24, 1983. Laboratory examinations on admission showed severe anemia and renal dysfunction. Every possible treatment was done in order to improve the laboratory data preoperatively. Another big problem in this case of hemodialyzed patient was brain edema and bleeding tendency. In order to cope with brain edema, intravenous administration of glycerol and slow hemodialysis for three days were performed preoperatively. These treatments were thought to be effective to reduce bleeding tendency also. During operation, however, heavy swelling of the cerebellum forced us to resect one third of the hemisphere to remove the tumor totally. In addition to this, postoperative mild bleeding in the cavity after tumor resection, subcortical hemorrhage around the shunt tube and oozing from the wound were observed. The patient was discharged from the hospital four months after surgery without any neurological deficit. The way of recovery, however, was not uneventful, because the patient developed various kinds of postoperative complications as mentioned above. In the postoperative managements, we felt almost as if we were treading on thin ice. Neurosurgical management in hemodialyzed patients is not yet very common. We should improve the postoperative management by adding new experience with similar cases.

Adult↗
PubMed1983

Toxicologic evaluation of metronidazole with particular reference to carcinogenic, mutagenic, and teratogenic potential.

The gastrointestinal tract and nervous system are the main targets for metronidazole toxicity. With the possible exception of certain neurotoxic effects in a few heavily treated patients, all the toxic effects of metronidazole are transient and reversible on withdrawal of the drug. Properly designed tests for embryotoxicity and teratogenicity in rats, rabbits, and mice have produced convincingly negative results, and no adverse effects on the fetus have been observed in women given the drug for trichomoniasis during various stages of pregnancy. The antimicrobial activity of metronidazole is thought to depend on its nitroreduction to form short-lived cytotoxic metabolites capable of reacting with deoxyribonucleic acid. It is therefore perhaps not surprising that metronidazole has been reported to be mutagenic for certain strains of Salmonella typhimurium. Metronidazole gave negative results in the mouse micronucleus test and no increase in sister chromatid exchanges or chromosomal aberrations in cultured human lymphocytes. Prolonged exposure to metronidazole in the treatment of patients with Crohn's disease was not associated with any increase in the frequency of chromosomal aberrations. Prolonged high-dose exposure of mice to metronidazole led to an increased incidence of lung tumors in three separate studies and to a suggestive increase in lymphoreticular neoplasia in female animals in one of the studies. These effects are probably nonspecific, since major effects on the incidence of neoplasms of the same and other kinds have been produced by merely varying the amount of a standard diet that mice consume. A reported excess of liver tumors in rats exposed to metronidazole can be explained by the fact that the authors failed to age standardize their data despite a big and highly significant beneficial effect of the drug on survival. Two carcinogenicity studies in hamsters have given entirely negative results. The follow-up for 10 or more years of 771 women first treated with metronidazole between 1960 and 1969 for trichomoniasis revealed no excess of any form of cancer attributable to treatment, and no excess cancer risk has so far come to light in the Kaiser-Permanente follow-up of nearly 2500 patients given at least one prescription of metronidazole between 1969 and 1973. At the present time it is reasonable to conclude that this highly useful, and sometimes life-saving, drug is essentially free of cancer risk or other serious toxic side effects.

Abnormalities, Drug-Induced↗
PubMed1992

Biochemical properties of endothelin converting enzyme in renal epithelial cell lines.

This is the first report clearly demonstrating the presence of endothelin (ET) converting enzyme (ECE) in non-vascular cells (renal epithelial cell lines, MDCK and LLC-PK1). ECEs derived from these epithelial cells were very similar to the endothelial ECE in the following biochemical properties: 1) The optimum pH was 7.0; 2) the Km value for big ET-1 was approximately 30 microM; 3) the enzyme was potently inhibited by EDTA, o-phenanthroline and phosphoramidon; and 4) the enzyme did not convert big ET-2 or big ET-3. These data suggest that phosphoramidon-sensitive ECE is involved in the processing of big ET-1 to ET-1 in the renal tubule.

Animals↗
PubMed1991

Phosphoramidon inhibits the conversion of intracisternally administered big endothelin-1 to endothelin-1.

It is suggested that endothelin-1 (ET-1), a potent vasoconstrictor peptide, is involved in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). We examined the effects of intracisternal administration of big ET-1 on the cerebral arteries in the absence or presence of pretreatment with phosphoramidon, an inhibitor of ET converting enzyme, in anesthetized dogs. After intracisternal administration of big ET-1 (10 micrograms/dog), the caliber of the basilar artery on the angiogram was decreased to about 59% of the control. This was accompanied by a marked increase in immunoreactive ET in the cerebrospinal fluid. Systemic arterial pressure was markedly elevated following big ET-1 injection. All changes induced by big ET-1 were effectively prevented with phosphoramidon. These data suggest that intracisternally administered big ET-1 is converted to ET-1 and that the generated ET-1 produces cerebral vasospasm and hypertension. A phosphoramidon-sensitive metalloproteinase appears to contribute to this conversion.

Animals↗
PubMed2004

Towards understanding assessments of the big five: multitrait-multimethod analyses of convergent and discriminant validity across measurement occasion and type of observer.

Multitrait-multimethod analyses were used to examine the degree of convergent and discriminant validity of the Big Five. Phase 1 examined self-reports of the Big Five across three measurement occasions. Self-reports of the Big Five traits were stable, but were moderately intercorrelated. Phase 2 examined assessments of the Big Five across different types of informants (self, peer, and parent). Assessments converged across types of informants and, importantly, there was no evidence of correlation between the Big Five traits across the perspectives of different types of informants. The present results suggest that the degree of orthogonality of the Big Five traits depends on the source of the data. A single informant produces Big Five traits that are intercorrelated, whereas diverse informants tend to produce a much more orthogonal structure. Discussion focuses on methodological considerations in examining levels of convergent and discriminant validity and the theoretical implications for understanding personality assessments and the relationship between three-and five-factor models of personality.

Adolescent↗
PubMed2003

Big Five factors of personality and replicated predictions of behavior.

Measures of the Big Five factors of personality were used to predict a variety of criterion variables thought to represent behaviors of some social and cultural significance (e.g., alcohol consumption, grade point average). Analyses focused on replicated predictions across 2 independent samples of participants (Ns = 276 and 142) with 3 different measures of the Big Five (the NEO Five-Factor Inventory, the Revised NEO Personality Inventory, and the Five-Factor Nonverbal Personality Questionnaire, the latter an experimental nonverbal personality inventory). The results indicated substantial consistency in behavior predictions across the different Big Five assessments. The data are interpreted as supporting both the construct validity of the personality measures used and the role of the Big Five factors as determinants of certain complex behaviors.

Female↗
PubMed1999

Perioperative plasma endothelin-1 and Big endothelin-1 concentrations in elderly patients undergoing major surgical procedures.

UNLABELLED: Plasma concentrations of the vasoconstrictor endothelin-1 (ET-1) increase during acute physiologic stress, but the role of ET-1 in the pathophysiology of stress remains largely undefined. Whether ET-1 mediates thermoregulatory changes in vasomotor tone is unknown. ET-1 and its more stable precursor, Big ET-1, were measured in plasma obtained at several perioperative time points from 95 consecutive elderly patients (mean age 70 +/- 1 yr) randomized to receive either normothermic or hypothermic perioperative care while undergoing major surgical procedures. In the postoperative period, there were no significant changes in plasma ET-1 concentrations, but Big ET-1 concentrations increased considerably (P < 0.0001). There were no significant differences in mean ET-1 or Big ET-1 levels in normothermic and hypothermic patients. Preoperative and postoperative ET-1 concentrations were significantly higher in patients with a history of hypertension (P < 0.002) and in those requiring treatment for postoperative hypertension (P < 0.003). Patients with cancer and those undergoing abdominal surgery had significantly higher Big ET-1 concentrations (P < 0.0001 and P < 0.003, respectively). These data support the hypothesis that Big ET-1 is a more sensitive measure of endothelin system activation after major surgery. Premorbid conditions and location and type of surgery influence perioperative ET-1/Big ET-1 concentrations. IMPLICATIONS: The endothelin response seems to be significantly associated with perioperative hemodynamic aberrations. The endothelin-1 (ET-1) precursor Big ET-1 is a more sensitive measure of the endothelin system activation in response to surgical stress than ET-1 alone. Thermoregulatory vasoconstriction in response to mild perioperative hypothermia occurs independently of the endothelin system.

Abdomen↗
PubMed2004

Disease registries provide performance boost without big cost.

There is a fairly simple and low-cost way of computerizing some patient data that is having a big payoff for practices in terms of improving performance and quality. Disease registries are databases that allow practices to track patients with one or more chronic conditions, including diabetes, asthma, and congestive heart failure.

Chronic Disease↗
PubMed1993

Measurement techniques in animal locomotion analysis.

Animal performance can be determined by subjective observations or objective measurements. Numerical data are only then superior to results of subjective observations when they are the result of measurements carried out to test a well-defined hypothesis or to give the answer to a clear, precisely formulated question. In the analysis of kinematics a careful evaluation of the set-up of the measurement equipment and the resulting accuracy in the data is required. Measurements in three dimensions (3D) are theoretically better than those in 2D. Practically, however, collection, analysis, interpretation and presentation of 3D data are so much more complicated that frequently 2D analysis appears to be more useful. The minimal size of markers necessary to obtain a certain accuracy in kinematic data is usually too big for practical use. Smaller markers impair accuracy. Reduction of measurement noise is obligatory when time derivatives are to be calculated. Skin movement artefacts cannot be removed by data smoothing. Forces occurring between the digits and the ground can be determined using a force plate or an instrumented shoe. A force plate is accurate, but repeated trials are necessary. Using a force shoe each ground contact results in useful data. However, the shoe itself may affect locomotion. Surface strains on long bones can be recorded relatively easily. Determination of loading forces from surface strains is complicated but can be carried out using multiple strain gauges and a post-mortem calibration test. Strain in tendons is difficult to measure due to problems in defining a'zero' or reference length.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Husbandry↗
PubMed1998

Direct enzyme immunometric measurement of plasma big endothelin-I concentrations and correlation with indicators of left ventricular function.

Recent studies have suggested that the plasma concentrations of endothelin-1, a potent vasoconstrictive peptide, are increased in patients with congestive heart failure. This study aimed to evaluate a new direct ELISA for big endothelin-1 (the precursor of endothelin-1), in comparison with a big endothelin-1 ELISA using plasma sample extraction, and to investigate whether plasma big endothelin-1 concentrations correlate with indicators of left ventricular function. The direct ELISA yielded significantly (P < 0.001) lower results than the assay with extracted samples (0.9 +/- 0.5 pmol/L vs 2.7 +/- 1.9 pmol/L; n = 90); however, the results of the two assays were closely correlated (r = 0.86, P < 0.001). Plasma big endothelin-1 concentrations exhibited a significant (P < 0.001) negative correlation (r = -0.46, r = -0.40) with the left ventricular ejection fraction and a significant positive correlation (r = 0.40, P < 0.001; r = 0.36, P < 0.01) with the left ventricular end-diastolic pressure and the left ventricular end-diastolic (r = 0.42, r = 0.38, P < 0.001) and end-systolic (r = 0.52, r = 0.47, P < 0.001) volume indices. Plasma big endothelin-1 concentrations were notably greater in patients with New York Heart Association (NYHA) class II-IV symptoms than in patients without cardiac disease or in patients categorized to NYHA class I. These data suggest that plasma big endothelin-1 concentrations, measured by a direct ELISA, correlate with hemodynamic indicators and symptoms of left ventricular dysfunction.

Adult↗