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PubMed2003

[The shaping of ethical approach to medical experimentation in Poland].

Contemporary awareness of bioethical norms in treatment and research experiments in medicine underwent a long evolution in Poland. The process was similar to that of other countries developing this kind of research. The negative experiences of World War II resulted in tendency to curb experimentation on humans. The seventies witnessed a heated discussion leading to settlement of this problem. The argument was that stringent limitations on such experiments would stop the development of new, indispensable drugs. This discussion also reached Poland where the majority of participants were doctors and lawyers expressing their views mostly in the press. This led in consequence to the establishment of the first ethical norms in medical experiment on humans. These were expressed in subsequent codes of ethics for the medical profession as well as in the founding of the first bioethical commissions at medical schools. Currently such norms based on the so-called "good clinical practice" standards were incorporated in the legal acts that establish bioethical committees at medical schools and other medical institutes. This paper also presents some specific aspects of research on female patients.

Bioethical Issues↗

PubMed2003

Cyclic allene intermediates in intramolecular dehydro Diels-Alder reactions: labeling and theoretical cycloaromatization studies.

A comprehensive theoretical and experimental investigation of dehydro Diels-Alder reactions examining the evolution of the cyclic allene intermediates under conditions for intramolecular and ionic and radical intermolecular cycloaromatization processes is reported. Theoretical calculations showed that the most favored intramolecular path for cycloaromatization of 1,2,4-cyclohexatriene 4 and its benzoannulated derivative 14, strained cyclic allenes, consists of a pair of successive [1,2] H shifts rather than a [1,5] shift. Cycloaromatization of cyclic allenes may follow both inter- and intramolecular pathways, depending on the experimental conditions (use of protic or aprotic solvents). For synthetic purposes, the best procedure is to use a protic solvent to promote the ionic intermolecular route, the fastest and highest yielding. When the reaction is carried out in CCl4, intermolecular radical addition of chlorine to the cyclic allene competes with intramolecular aromatization paths. Theoretical calculations predict a low barrier for the reaction of cyclic allenes with carbon tetrachloride, and that the cyclic allenes act as nucleophiles in this reaction.

Journal Article↗

PubMed1994

Animal lectins as self/non-self recognition molecules. Biochemical and genetic approaches to understanding their biological roles and evolution.

In recent years, the significant contributions from molecular research studies on animal lectins have elucidated structural aspects and provided clues not only to their evolution but also to their multiple biological functions. The experimental evidence has suggested that distinct, and probably unrelated, groups of molecules are included under the term "lectin." Within the invertebrate taxa, major groups of lectins can be identified: One group would include lectins that show significant homology to membrane-integrated or soluble vertebrate C-type lectins. The second would include those beta-galactosyl-specific lectins homologous to the S-type vertebrate lectins. The third group would be constituted by lectins that show homology to vertebrate pentraxins that exhibit lectin-like properties, such as C-reactive protein and serum amyloid P. Finally, there are examples that do not exhibit similarities to any of the aforementioned categories. Moreover, the vast majority of invertebrate lectins described so far cannot yet be placed in one or another group because of the lack of information regarding their primary structure. (See Table 1.) Animal lectins do not express a recombinatorial diversity like that of antibodies, but a limited diversity in recognition capabilities would be accomplished by the occurrence of multiple lectins with distinct specificities, the presence of more than one binding site, specific for different carbohydrates in a single molecule, and by certain "flexibility" of the binding sites that would allow the recognition of a range of structurally related carbohydrates. In order to identify the lectins' "natural" ligands, we have investigated the interactions between those proteins and the putative endogenous or exogenous glycosylated substances or cells that may be relevant to their biological function. Results from these studies, together with information on the biochemical properties of invertebrate and vertebrate lectins, including their structural relationships with other vertebrate recognition molecules, are discussed.

Animals↗

PubMed2006

Spinal motoneuron synaptic plasticity during the course of an animal model of multiple sclerosis.

During the course of experimental autoimmune encephalomyelitis, a massive loss of motor and sensitive function occurs, which has been classically attributed to the demyelination process. In rats, the clinical signs disappear within 5 days following complete tetraplegia, indicating that demyelination might not be the only cause for the rapid evolution of the disease. The present work investigated the occurrence of experimental autoimmune encephalomyelitis-induced changes of the synaptic covering of spinal motoneurons during exacerbation and after remission. The terminals were typed with transmission electron microscopy as C-, F- and S-type. Immunohistochemical analysis of synaptophysin, glial fibrillary acidic protein and the microglia/macrophage marker F4/80 were also used in order to draw a correlation between the synaptic changes and the glial reaction. The ultrastructural analysis showed that, during exacerbation, there was a strong retraction of both F- and S-type terminals. In this sense, both the covering as well as the length of the remaining terminals suffered great reductions. However, the retracted terminals rapidly returned to apposition, although the mean length remained shorter. A certain level of sprouting may have occurred as, after remission, the number of F-terminals was greater than in the control group. The immunohistochemical analysis showed that the peak of synaptic loss was coincident with an increased macro- and microglial reaction. Our results suggest that the major changes occurring in the spinal cord network during the time course of the disease may contribute significantly to the origin of the clinical signs as well as help to explain their rapid recovery.

Animals↗

PubMed2005

Delay of intracortical bone remodelling following a stress change: a theoretical and experimental study.

BACKGROUND: A theoretical model and an experimental setup were specifically designed to identify and determine the delay of the cortical bone response (restricted to mineralization and demineralization) to a stress change. METHODS: The in vivo experiment considered two groups of rats: a running group and a control sedentary group. The running group rats were compelled to a running activity for 15 weeks, followed by a sedentary activity for 15 weeks. Bone density was derived from hardness measurements. The parameters of the remodelling theory, including the response delay and the remodelling rates, were determined from these experimental measurements. FINDINGS: Bone density increased significantly during the activity period, and decreased rapidly when rats returned to sedentary state. The identification of the model's parameters produced evolution curves that were within the limits of the standard deviation of the experimental data. The densification rate was lower than the resorption rate, and the densification delay was greater than bone resorption delay. INTERPRETATION: The delays determined with this macroscopic model are related to response delays due to biological internal processes in bone.

Adaptation, Physiological↗

PubMed2006

Numerical analysis and experimental results of high-power Er/Pr:ZBLAN 2.7 microm fiber lasers with different pumping designs.

Gain factor and output performance of erbium-praseodymium codoped ZBLAN double-clad fiber lasers at 2.7 microm with different pumping designs were calculated and analyzed. Single-end backward pumping with a highly reflective mirror butted against one fiber end and dual-end pumping with Fresnel reflections from both fiber ends were found to be the most efficient pumping designs. Ten-watt-level Er/Pr:ZBLAN fiber lasers proved to be achievable with recent diode laser and ZBLAN fiber technologies. Their corresponding optimum fiber lengths for different pumping configurations were determined. It was also found that fiber lasers with a flat evolution of gain factor can obtain the largest output power. Experimental results of 4 m and 12 m fiber lasers showed very good agreement with simulation results.

Journal Article↗

PubMed1994

[Evaluation of an experimental model of multiple organ dysfunction].

OBJECTIVE: To perform an experimental model of Multiple Organ Dysfunction Syndrome (MODS) without employing bacteria or endotoxin stimulus and to follow its evolution in vivo by a Computerized Tomography analysis of the lungs. DESIGN: Rats were submitted to intraperitoneal injection of a 2.5% zymosan suspension in mineral oil (1 g/kg weight) or mineral oil alone; control rats received no treatment. METHODS: The observation period was 15 days. During this period symptoms and survival were noticed daily. CT scans of lungs were made at the 7th and 14th days; data were post-processed to obtain information on lung density. The rats were sacrificed at the 15th day by heart puncture; blood was utilized for determination of hemochrome, differential leukocyte count, thrombocytes, glycemia, uremia, bilirubin. Lungs, liver, spleen and kidney were dissected and weighted for determination of relative organ weight. DATA ANALYSIS: Data were compared by "t" Student's test for impaired data and Fisher Exact test. RESULTS: Symptoms, survival, blood analysis and relative organ weight agreed with a progressive, ingravescent, triphasic illness caused by a systemic inflammatory response involving remote organ too. The CT study proved able to monitoring and analyzing organ damage: a temporal sequence of evolution of damage exists; organ damage is localized in microcirculatory system (density augment) and in parenchyma (morphologic alterations and fibrosis). DISCUSSION: The described experimental model reproduces a MODS-like illness in zymosan receiving rats; the CT scan is effective to evaluate the evolution of organ damage.

Animals↗

PubMed1982

Selection at the alpha-Gpdh locus in experimental populations of Drosophila melanogaster.

Three sets of experiments have been conducted in order to evaluate the role of natural selection at the alpha-Gpdh locus in Drosophila melanogaster. (1) The evolution of the F-allele frequency has been followed for many generations in 13 experimental populations having different genetic backgrounds. (2) Egg-to-adult viability has been measured in synthetic populations derived from one locality (Brouilly) and the results have been compared with those of a previous experiment involving a different local population (Tostes). (3) The effects of sodium octanoate on egg-to-adult viability have been measured on the genotypes FF, FS, SF, and SS. The results demonstrate that selection operates on a small block of genes which includes the alpha-Gpdh locus.

Alleles↗

PubMed2005

Heterogeneous proliferation within engineered cartilaginous tissue: the role of oxygen tension.

This article investigates heterogeneous proliferation within a seeded three-dimensional scaffold structure with the purpose of improving protocols for engineered tissue growth. A simple mathematical model is developed to examine the very strong interaction between evolving oxygen profiles and cell distributions within cartilaginous constructs. A comparison between predictions based on the model and experimental evidence is given for both spatial and temporal evolution of the oxygen tension and cell number density, showing that behaviour for the first 14 days can be explained well by the mathematical model. The dependency of the cellular proliferation rate on the oxygen tension is examined and shown to be similar in size to previous work but linear in form. The results show that cell-scaffold constructs that rely solely on diffusion for their supply of nutrients will inevitably produce proliferation-dominated regions near the outer edge of the scaffold in situations when the cell number density and oxygen consumption rate exceed a critical level. Possible strategies for reducing such non-uniform proliferation, including the conventional methods of enhancing oxygen transport, are outlined based on the model predictions.

Cartilage↗

PubMed2002

Simultaneous diffusion MRI measurements from multiple perfused rat hippocampal slices.

Rat brain slices provide a controllable tissue model in which to investigate the biophysical basis of diffusion-weighted magnetic resonance (MR) signal changes observed clinically in nervous tissue after ischemic injury. This study describes a new multislice perfusion chamber that allows for the simultaneous acquisition of diffusion-weighted MR images from multiple perfused rat hippocampal slices (eight slices in the present study). These images had a signal-to-noise ratio (SNR) of 48 +/- 3 at b = 8080 s/mm(2), which was sufficient to analyze the multicomponent diffusion properties of water in rat hippocampal slices. The tissue water diffusion parameters (f(fast) = 0.527 +/- 0.041, D(fast) = 1.268 +/- 0.087 x 10(-3) mm(2)/s, and D(slow) = 0.060 +/- 0.003 x 10(-3) mm(2)/s) were stable for at least 8 hr after slice procurement (ANOVA, P > 0.05), suggesting that it may be possible to study the acute temporal evolution of diffusion changes in multiple brain slices following experimental perturbation.

Analysis of Variance↗

PubMed1986

The major histocompatibility complex of tassel-eared squirrels. II. Genetic diversity associated with Abert squirrels.

The extent of polymorphism and the rate of divergence of class I and class II sequences mapping to the mammalian major histocompatibility complex (MHC) have been the subject of experimentation and speculation. To provide further insight into the evolution of the MHC we have initiated the analysis of two geographically isolated subspecies of tassel-eared squirrels. In the preceding communication we described the number and polymorphism of TSLA class I and class II sequences in Kaibab squirrels (S. aberti kaibabensis), which live north of the Grand Canyon. In this report we present a parallel analysis of Abert squirrels (S. aberti aberti), which live south of the Grand Canyon in northern Arizona. Genomic DNA from 12 Abert squirrels was digested with restriction enzymes, electrophoresed, blotted, and hybridized with DR alpha, DR beta, DQ alpha, DQ beta, and HLA-B7 probes. The results of these hybridizations were remarkably similar to those obtained in Kaibab squirrels. The majority of class I and class II bands were identical in size and number, suggesting that Abert and Kaibab squirrels have not significantly diverged in the TSLA complex despite their geographical separation. Relative polymorphism of class II sequences was similar to that observed with Kaibab squirrels: beta sequences exhibited higher polymorphism than alpha sequences. As in Kaibab squirrels, a number of alpha and beta sequences were apparently carried on the same fragments. In comparison to class II beta sequences, there was limited polymorphism in class I sequences, although a diverse number of class I genotypes were observed. Attempts to identify segregating TSLA haplotypes were futile in that the only families of sequences with concordant distributions were DQ alpha and DQ beta. These observations and those obtained with Kaibab squirrels suggest that the present-day TSLA haplotypes of both subspecies are derived from a limited number of common, progenitor haplotypes through repeated intra-TSLA recombination.

Animals↗

PubMed1983

Transformation of oligodendroglia: a para- or preneoplastic effect of ethylnitrosourea on mouse brain.

The aim of this EM study was to assess the relationship of demyelination changes induced in mouse brain by a carcinogenic substance to the early steps in the evolution of neoplastic disease. The investigation on the 25 experimental mice injected at various stages of age with ethylnitrosourea revealed demyelination foci in three animals and interfascicular nests of abnormal cells in seven animals, the latter most probably being of oligodendroglial origin. The nest cells were characterized by their large size and a multitude of interdigitated cytoplasmic processes forming complicated membranous patterns. The abnormal development of oligodendroglial cytoplasmic processes is considered to be the cause of the demyelination. This previously unknown form of oligodendroglial transformation may consist in either the earliest preneoplastic changes or represent a reactive, paraneoplastic type of alteration.

Animals↗

PubMedDate not supplied

Enantiomer enrichment in early peptides.

The two main ordered conformations of polypeptides, the alpha-helix and the beta-sheet, were considered as possible asymmetric supports for stereoselective processes leading to the enrichment in one enantiomer. alpha-Helices can accommodate residues of both chirality distributed in the same chain, whereas the formation of beta-sheets arises from the association of chain segments containing at least seven residues of the same chirality. When the residue composition departs from the racemic mixture, one handedness of the helix is favored, whereas the beta-sheet nuclei become predominantly of a unique chirality. Taking into account these observations, processes of enrichment specific for alpha- amd beta-structures were envisaged theoretically theoretically as well as experimentally.

Biological Evolution↗

PubMed2000

Evolutionary dynamics of HTLV-I.

Using mathematical models to describe the in vivo dynamics of HTLV-I infection, an explanation is offered for the slow rate of evolution of HTLV-I relative to HIV-1. In agreement with experimental findings, it is assumed that cell activation is required for successful replication in T helper cells and that HTLV-I induces a significant degree of bystander activation. It is found that the rate of evolution of HTLV-I is limited by the restricted availability of activated uninfected T cells, both at high and low proviral loads. This limits the within-host sequence diversity of HTLV-I and may therefore account for the slow rate of evolution of the virus in the population. Specific differences in the in vivo dynamics of HTLV-I and HIV-1 are identified which may account for the discrepancy in the rate of evolution of these two retroviruses.

Evolution, Molecular↗

PubMed2005

Substitution of thoracic oesophagus by interposition of a pedicled gastric tube, preserving LES function: clinical and histological follow-up.

Assessment of clinical evolution and histological findings in a group of animals experimentally operated on to substitute the thoracic oesophagus with a gastric tube. Six piglets underwent oesophageal replacement with a gastric tube, constructed from the greater curvature of stomach and pedicled on the gastroepiploic vessels, which was interposed between the oesophageal stumps. At follow-up, all animals were found to be growing and eating normally, apart from case no 1 (stenosis of the lower oesophageal anastomosis). Ph-metry showed a neutral pH on the gastric tube. Postmortem histological analysis of the gastric tube and native oesophagus samples did not show any significant lesions, except in case no 1 (inflammation of the gastric tube and upper oesophagus due to food stasis). The technique of substitution of the oesophagus with an interposed pedicled gastric tube can be a breakthrough in existing surgical methods of oesophageal replacement.

Animals↗

PubMed1989

Porphyrin-proteinoid complexes as models of prebiotic photosensitizers.

Photochemical activity as well as some spectral properties of various porphyrins and their model complexes with proteinoids were studied. Photochemical activity increased from the less advanced biosynthetic chlorophyll precursors to the more advanced compounds. The significant increase was detected as a result of the formation of complexes of phytol-containing porphyrins with proteinoids, which brings about the disaggregation of the pigment clusters formed in the aqueous environment. Hemin is photochemically inactive, either alone or in complex with proteinoid. Although hemoproteinoid was demonstrated to be able to catalyse photochemical electron transfer, its activity is about 20 times lower when compared with the chlorophyll a-proteinoid complex. Experimental results are discussed in context of the early evolution of photosynthesis.

Chlorophyll↗

PubMed2004

Volumetric evaluation of the ischemic lesion size with serial MRI in a transient MCAO model of the rat: comparison of DWI and T1WI.

Magnetic resonance imaging (MRI) is applied in many studies on experimental cerebral ischemia in rodents to monitor the temporal evolution of ischemic damage. We report a protocol to evaluate the infarct size after middle cerebral artery occlusion with reperfusion (MCAO/R) in male Wistar rats. Imaging was performed with a 2.35 T scanner and we focused on diffusion-weighted imaging (DWI), T2-weighted imaging (T2WI) and postcontrast T1-weighted imaging (T1WI). We show the detailed procedure of volumetry, the contrast-to-noise ratio (CNR) and the intraindividual variability of infarct and hemispheric volumes at different reperfusion times. The presented method is of low variability if image contrast between ischemic and nonischemic tissue is very high, which is the case not only for all sequences at 8 and 12 h of reperfusion but also for DWI after 3 and 5 h of reperfusion. Furthermore, we describe the so-called mismatch region of lesion sizes depicted on DWI and postcontrast T1WI that suffers from cytotoxic edema but lacks contrast enhancement.

Animals↗

PubMed2004

Multiple time scales and subsystem embedding in the learning of juggling.

To gain insight into the multiform dynamics and integration of remote yet pertinent subsystems into the performance of complex perceptual-motor skills, we recently conducted a series of longitudinal and cross-sectional experiments on the acquisition of 3-ball cascade juggling in which we measured, next to the ball trajectories, postural sway, eye and head movements and respiration. The aim of the present paper is to review the main results and theoretical implications of these experimental studies for understanding skill acquisition. As regards the evolution of the quality of the juggling itself, we found that only certain aspects of throwing and catching were adjusted, while the goal behavior of sustained juggling (operationalized as the number of consecutive throws) and the degree of frequency and phase locking between the ball trajectories, indexing pattern stability, increased monotonically. The latter three aspects evolved at different rates, reflecting the existence of a temporal hierarchy in learning. Postural sway exhibited initial manifestations of task-specific, possibly mechanically induced, modes of 3:1 and 3:2 frequency locking with the ball trajectories and only few transitions between those modes. Functional stability appeared to be enhanced during practice by minimizing the sway amplitudes rather than by adjusting the sway dynamics itself. Eye and point-of-gaze movements also showed instances of 3:1 and 3:2 frequency locking with the ball trajectories; especially establishing a 3:1 locking (horizontal eye movements) appeared to be important. Expert behavior suggested that extended practice promotes reliance on multiple sources of information, allowing the proficient juggler to switch adaptively between functional organizations involving distinct perceptual systems. No consistent coordination between breathing and juggling was found. It was concluded that multiform dynamics, involving hierarchically ordered time scales, underlie the acquisition of complex skills and that the subsystems subserving realization of the task goal become assembled and embedded in a task- and subsystem-specific manner.

Cross-Sectional Studies↗