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Biomedical subjects

V Albrecht

Publications and source records attributed to V Albrecht.

At least 19 recordsLinked to original sources

Photothrombic activity of m-THPC-loaded liposomal formulations: pre-clinical assessment on chick chorioallantoic membrane model.

The objective of this study was to evaluate the ability of meso-tetra(hydroxyphenyl)chlorin (m-THPC) encapsulated into liposomal formulations to occlude neovascularization. Two m-THPC formulations including conventional or plain liposomes (Foslip) based on dipalmitoylphosphatidylcholine (DPPC) and the corresponding long-circulating poly(ethylene glycol) (PEG)-modified liposomes (PEGylated liposomes: Fospeg) were evaluated as delivery systems. Using the chick chorioallantoic membrane (CAM) as in vivo model, the fluorescence pharmacokinetic behaviour of encapsulated m-THPC reflecting the rate of the extravasation of the dye from the CAM vasculature and its photothrombic effectiveness were determined. This study was focused on the influence of the drug and/or light doses on the mean retention time of m-THPC within the CAM blood vessels after intravenous injection, and its photothrombic efficacy. Irrespective of the formulations tested and the drug doses injected, similar fluorescence pharmacokinetic profiles were obtained. The fluorescence contrast reached a steady state 30 s after injection. Constant positive values of the fluorescence contrast suggest that m-THPC is confined into the intravascular compartment during the experimental time (500 s). However, the photodynamic therapy assays showed that Foslip appears to be less potent than Fospeg in terms of photothrombic activities on the CAM model. For instance, the light dose necessary to induce the desired vascular damage with Foslip was twice (100 J/cm2) higher than with Fospeg (50 J/cm2). It can be inferred that this pre-clinical study showed that the formulation based on PEGylated liposomes technology offers a suitable delivery system for the treatment of choroidal neovascularization associated with age-related macular degeneration.

1,2-Dipalmitoylphosphatidylcholine↗

Characterization of a T-DNA insertion mutant for the protein import receptor atToc33 from chloroplasts.

In Arabidopsis thaliana, the Toc34 receptor component of the chloroplast import machinery is encoded by two independent but highly homologous genes, atToc33 and atToc34. We have isolated a T-DNA insertion mutant of atToc33 which is characterized by a pale phenotype, due to reductions in the levels of photosynthetic pigments, and alterations in protein composition. The latter involve not only chloroplast proteins but also some cytosolic polypeptides, including 14-3-3 proteins which, among other functions, have been proposed to be cytosolic targeting factors for nucleus-encoded chloroplast proteins. Within the chloroplast, many, though not all, proteins of the photosynthetic apparatus, as well as proteins not directly involved in photosynthesis, are found in significantly reduced amounts in the mutant. However, the accumulation of other chloroplast proteins is unaffected. This suggests that the atToc33 receptor is responsible for the import of a specific subset of nucleus-encoded chloroplast proteins. Supporting evidence for this conclusion was obtained by antisense repression of the atToc34 gene in the atToc33 mutant, which results in an exacerbation of the phenotype.

Arabidopsis↗

The NAF domain defines a novel protein-protein interaction module conserved in Ca2+-regulated kinases.

The Arabidopsis calcineurin B-like calcium sensor proteins (AtCBLs) interact with a group of serine-threonine protein kinases (AtCIPKs) in a calcium-dependent manner. Here we identify a 24 amino acid domain (NAF domain) unique to these kinases as being required and sufficient for interaction with all known AtCBLs. Mutation of conserved residues either abolished or significantly diminished the affinity of AtCIPK1 for AtCBL2. Comprehensive two-hybrid screens with various AtCBLs identified 15 CIPKs as potential targets of CBL proteins. Database analyses revealed additional kinases from Arabidopsis and other plant species harbouring the NAF interaction module. Several of these kinases have been implicated in various signalling pathways mediating responses to stress, hormones and environmental cues. Full-length CIPKs show preferential interaction with distinct CBLs in yeast and in vitro assays. Our findings suggest differential interaction affinity as one of the mechanisms generating the temporal and spatial specificity of calcium signals within plant cells and that different combinations of CBL-CIPK proteins contribute to the complex network that connects various extracellular signals to defined cellular responses.

Amino Acid Sequence↗

Novel protein kinases associated with calcineurin B-like calcium sensors in Arabidopsis.

Members of the Arabidopsis calcineurin B-like Ca(2)+ binding protein (AtCBL) family are differentially regulated by stress conditions. One AtCBL plays a role in salt stress; another is implicated in response to other stress signals, including drought, cold, and wounding. In this study, we identified a group of novel protein kinases specifically associated with AtCBL-type Ca(2)+ sensors. In addition to a typical protein kinase domain, they all contain a unique C-terminal region that is both required and sufficient for interaction with the AtCBL-type but not calmodulin-type Ca(2)+ binding proteins from plants. Interactions between the kinases and AtCBLs require micromolar concentrations of Ca(2)+, suggesting that increases in cellular Ca(2)+ concentrations may trigger the formation of AtCBL-kinase complexes in vivo. Unlike most serine/threonine kinases, the AtCBL-interacting kinase efficiently uses Mn(2)+ to Mg(2)+ as a cofactor and may function as a Mn(2)+ binding protein in the cell. These findings link a new type of Ca(2)+ sensors to a group of novel protein kinases, providing the molecular basis for a unique Ca(2)+ signaling machinery in plant cells.

Amino Acid Sequence↗

Global dimensional complexity of the EEG in healthy volunteers.

In contrast to the single-channel dimensional complexity, the global dimensional complexity is calculated from a multichannel EEG. The intention with the method is to measure the spatial distribution of information processing in the brain. The method seems to be of interest in psychopharmacological research, but the interpretation of the results in physiological terms is rather difficult. To get a more detailed information on the physiological significance of the EEG complexity measures, the influence of well-known physiological factors was studied in a group of 14 healthy subjects aged from 1.5 to 61 years. It was found that the correlation dimension was somewhat higher in older individuals, but the correlation with age was not statistically significant. However, the global correlation dimension was significantly lower during full alertness than during drowsiness. These results might reflect the changes in spatial structure of information processing, a high complexity suggesting a 'disorganisation' during drowsiness. As regards the age-dependent changes of the correlation dimension, the spatial 'flexibility' of information processing was also studied, using the differences between the 'alert' and 'drowsy' parts of the same EEG as indicator. It was found that the differences 'drowsy minus alert' were significantly related to age. A plausible interpretation seems to be that the spatial distribution of information processing is more changeable, or more flexible, in adults than in children.

Adolescent↗

Dynamics of the effects of levoprotiline and maprotiline on EEG in patients with major depressive episodes (DSM-III-R).

The presented study compares the effect of the well-tested antidepressant maprotiline and a new antidepressant with an atypical pharmacological profile, levoprotiline, on EEG during repeated assessment after single dose administration. From the original number of 34 patients fulfilling the criteria of a major depressive episode (DSM-III-R) on account of a low-voltage record or pathological findings 11 were eliminated. To 12 of the remaining patients levoprotiline was administered and to 11 maprotiline, after a one-week placebo period, in doses of 150 mg. The EEG was recorded after an accommodation session immediately before, 1.5, 3, 4.5, 6 and 24 hours after a single dose administration. The record was taken on a 16-channel average reference montage at rest with closed eyes. Two-minute intervals were divided into 30 four-second periods at a sampling frequency of 128 Hz. From the signal by means of FFT the spectra were estimated and the mean spectrum for the entire recording was calculated. This was then divided into 10 frequency bands. The new method of frequency analysis of alpha-entropy was also used which is a global measure of the difference between two spectra. Three hours after administration of a single dose levoprotiline had an EEG profile corresponding to the profile of tricyclic antidepressants, i.e. it increased the values of the power spectra density in the region of 5-8.5 Hz and in the entire beta band; the decline of power in the alpha band was, however, absent. As regards maprotiline, 3 hours after administration a profile typical for antidepressants was not found; obviously because of the great variance of values of power spectra density as a result of great interindividual differences in the ingestion phase. Changes of the EEG spectrum expressed as values of alpha-entropy during different periods of apparently assessment are not incidental. After the initial rise of values a decline occurs.

Adult↗

Relationship between a long-term treatment of 2-mercaptoethanol and protein metabolism in the ageing rat.

Female RLEF1/Lati rats were chronically treated with 2-mercaptoethanol in a dose of 13 micrograms.100 g bw-1.day-1 dissolved in drinking water. During a 48-h experiment 15N-labelled glycine was given orally in a dose of 5 mg 15N.kg bw-1 and urine samples were collected and analysed by an emission spectrometric isotope method. Protein synthesis and nitrogen excretion rate constants were calculated according to the three-pool model, and 3-methylhistidine excretion rates were also determined. 2-Mercaptoethanol appears to influence protein metabolism; however, the slower rates of protein synthesis proved to be apparent in almost all groups of treated rats. Protein synthesis and nitrogen excretion rate constants have exceptionally high values in 2-year-old rats, possibly explained by the occurrence of hypercompensation mechanisms in old age. These were reflected by the excretion rates of 3-methylhistidine which were reduced as a result of sulphhydryl group interactions in age-dependent cellular metabolic changes.

Aging↗

[The effect of different protein diets on longevity and various biochemical parameters of aged rats].

In this work 23 month old rats were fed for 200 days with different protein diets (NT-diet: 19% protein, 72% of animal origin and LP-diet: 8.8% protein exclusively of vegetable origin). Some metabolic parameters and lifespan (on the base of a 50% death-rate) were determined. The relations of the liver free amino acids glycine + alanine and tyrosine + phenylalanine + branched chain amino acids and the ratio of phenylalanine/tyrosine were determined to be higher in the LP-group. Phenylalanine in liver and urea concentrations in liver and serum were lower in the LP-group. Furthermore the dopamine or serotonin levels were significantly lower in lateral and medial or lateral regions of the hypothalamus respectively in LP-diet fed rats. The norepinephrine content was not modified by the diets. The median lifespan of 23 month old rats was higher by 24% following LP-treatment. These results suggest that the protein component (amino acids) of different diets may modify metabolic parameters and lifespan of animals by mechanisms in which the central regulation may be involved.

Aging↗

The spectral dynamics and its applications in EEG.

The method of spectral dynamics is introduced to process slow changes in EEG. This method is based on evaluation of distance between EEG spectra. The typical application field is pharmaco-EEG after single dose drug administration, where distances between pre and post drug EEG spectra are computed. The distance between two spectra may be, however, defined in several different ways. The paper deals with the well known Lp metrics and with the metrics alpha that plays an important role in discriminating stationary processes with different spectra. The Lp and alpha metrics are non-equivalent and their properties, consistency and robustness, are studied in a simple statistical model.

Animals↗

Pharmacokinetics and tolerance of 7-methoxytacrine following the single dose administration in healthy volunteers.

7-methoxy-tetrahydroaminoacridine (7-MEOTA) is a new reversible cholinesterase inhibitor. Forty-eight young male volunteers divided into six dosage groups were included into a single-dose pharmacokinetic study with either oral (p.o.) or intramuscular (i.m.) administration. The dose of 7-MEOTA was 2, 4 or 8 mg/kg body weight p.o. or 0.5, 1 or 2 mg/kg body weight i.m. in the respective six dosage groups. The plasma levels data were fitted to an open one-compartmental model. The compound showed cholinomimetic adverse effects in 2 subjects with the blood levels exceeding 1,500 micrograms/l. The red blood cells levels paralleled those in plasma and were 2.5 times higher. The tmax was 4 hours and 1 h, t1/2 8.7 +/- 3.9 hours and 6.5 +/- 5.8 hours in case of p.o. and i.m. administration, respectively. The apparent clearance (D/AUC) was 5 times higher following p.o. administration, reflecting the differences in bioavailability.

Administration, Oral↗

[Epidemiologic study of symptoms of minimal brain dysfunction. 1. Design and testing of methods--the incidence of symptoms in the study group].

The authors inform on the elaboration of a screening method for recording of symptoms of minimal brain dysfunction and its initial verification in the research problem "Incidence of signs of minimal brain dysfunctions in children in the North Bohemian region". In the first stage a population group of children in the second form of primary school in three districts was examined, a total of 5080 children, and data were assembled from their 9000 parents. The authors describe the elaboration of the method which comprises rating scales which evaluate specific striking features in the behaviour, dysfunction in school skills (the forms were completed by teachers and mothers) and performance tests administered by the children themselves. Results of statistical analyses which confirmed the satisfactory consistency, composition, empirical and postdictive validity of the method are presented. The analyses revealed that the method used detects disorders included under the term of minimal brain dysfunctions and probably also disorders with the incidence of some identical symptoms (disorders of intellect, behavioural disorders in the wider sense of the word). The authors inform on the method of calculation and the ratio of the detected problem child population which was 14.8%. The group comprises 4.8% children which were unable to keep up with the first form of primary school and attend some special school. The method used detected, however, another 10% population with identical values. The authors discuss problems of screening diagnosis of specific developmental learning and behavioural disorders which form part of minimal brain dysfunctions. Problems associated with the evaluation of the assembled findings are discussed.

Attention Deficit Disorder with Hyperactivity↗

[Epidemiologic study of symptoms of minimal brain dysfunction: problems in quantitative evaluation].

The paper deals with problems arising during processing of data from an epidemiological screening focused on the Minimum Brain Dysfunction complex in children of the first and second form of elementary school. A new rating scale for the screening has been proposed. Its formal properties were analyzed in detail. Nontraditional coding of partial items forming the scale is discussed. Finally, statistical methods used for analysis of associations between the MBD scale and various combinations of aetiopathological variables are reviewed.

Attention Deficit Disorder with Hyperactivity↗

[What is the relation between pressure parameters and claudication distance?].

The authors examined the relationship between the ankle pressure, or pressure gradient on the one hand, and the walking distance and different actions, i.e. equalting and standing on tip toes, on the other hand. In 56 male patients with obliterating atherosclerosis, the first stage showed both pressure parameters as closely correlated to the final claudication distance, but not to the actions indicated above. At the second stage, 62 persons showed both the initial and final claudication distances as dependent on the poststenotic pressure as well as on the pressure gradient. Stepwise regression analysis showed a significant dependence of both distances on the lowest pressure measured on four crural arteries. The closest correlation [R = 0.98] was found between the initial and final claudication distances which persisted even after elimination of all pressure parameters.

Adult↗

[Ethical problems in modern genetics. Results of a questionnaire].

New findings on the possible application of DNA diagnosis in the prevention of hereditary diseases are associated also with ethical problems of medical genetics. A questionnaire programme evaluated the views of respondents (743) on four groups of questions: 1. state of information on health status, 2. examination of members of the family, 3. compulsory treatment, 4. preventive measures. The authors sought mutual associations between the replies to individual questions and characteristics of respondents. Development of medicine calls for interdisciplinary health education and the solution of newly arisen ethical and legal problems.

Attitude of Health Personnel↗