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Biomedical subjects

M Skalski

Publications and source records attributed to M Skalski.

At least 19 recordsLinked to original sources

Omega-3 polyunsaturated fatty acid enriched diet attenuates stress-induced lactacidemia in 10-day-old rats.

BACKGROUND: Lactacidemia is often seen under stress conditions including septic shock in the newborn. Under stress conditions, plasma catecholamine concentrations are increased and play an important role in lactate metabolism. Our previous study shows that perinatal feeding of omega-3 polyunsaturated fatty acid enriched diet (omega-3PUFA) attenuates lactacidemia of endotoxic shock in 10-day-old rats. In the omega-6 fatty acids series, decosapentanoic acid, two series prostaglandins and four series leukotrienes are synthesized through linoleic acids. As plasma lactate concentration correlates with the outcome of septic shock in the newborn, it is important to understand the effects of omega-3PUFA on lactate metabolism. Thus, we tested the hypothesis that perinatal feeding of omega-3 polyunsaturated fatty acid enriched diet (omega-3PUFA) alters responses to catecholamines and attenuates the stress-induced lactacidemia in 10-day-old rats. METHODS: Ten-day-old rats which perinatally fed omega-3PUFA. Lactacidemia was induced by swimming for 5 min. Ten-day-old rats which perinatally fed omega-6PUFA were controls. Omega-6 fatty acids series are contained in animal fats and corn oil. Adrenergic blockers were used to assess roles of catecholamines in swimming-induced lactacidemia. RESULTS: Swimming increased plasma lactate concentration less (P<0.05) in rats fed omega-3PUFA than rats fed omega-6PUFA. Swimming increased plasma concentrations of glucose and glucagon, cyclic adenosine monophosphate (cAMP) concentration and phosphoenolypruvate carboxykinase mRNA in the liver, and cAMP concentration in the hindlimb muscle more (P<0.05) in rats fed omega-3PUFA than in rats fed omega-6PUFA. Phentolamine and propranolol enhanced swim-induced lactacidemia in the omega-3PUFA group, while they decreased the lactacidemia in the omega-6PUFA group. Propranolol enhanced swimming-induced hyperglycemia in the omega-6PUFA group more than in the omega-3PUFA group. CONCLUSIONS: Omega-3PUFA might increase beta-adrenergic response in the liver and increase gluconeogenesis in response to stress, resulting in decreased lactacidemia.

Animals↗

Heterotopic expression of the Xl-Fli transcription factor during Xenopus embryogenesis: modification of cell adhesion and engagement in the apoptotic pathway.

In the Xenopus laevis embryo, the overexpression of the Xl-FLI protein, a transcription factor of the ETS family, provokes severe developmental anomalies, which affect anteroposterior and dorsoventral polarities, optic cup formation, head cartilage morphogenesis, and erythrocyte differentiation. It has been proposed that these effects could be correlated to modifications of cell adhesion properties and/or to an increased engagement of cells in the apoptotic pathway during early development (Remy et al., Int. J. Dev. Biol. 40, 577-589, 1996). To address these questions, we have first analyzed the behavior of cells overexpressing the protein in both aggregation and adhesion assays. We observe perturbations of cell-cell interactions as well as perturbations of cell adhesion and spreading on fibronectin and extracellular matrix (ECM). Second, we have analyzed apoptosis of cells overexpressing the Xl-FLI protein, by testing DNA fragmentation, caspase-3 activity and by performing TUNEL assay. We show that Xl-Fli overexpression results in the appearance of hallmarks of apoptosis, including exclusion of cells from the interior of the embryo, internucleosomal fragmentation of DNA and dose-dependent induction of caspase-3, resulting in the hydrolysis of poly(ADP-ribose) polymerase. In addition, a dominant-negative mutation of BMPs receptors decreases the effects of Xl-Fli overexpression, suggesting that a modification of the BMP signalling could be responsible for increased apoptosis. The latter appears to affect predominantly ventral and ventrolateral regions of the embryo.

Animals↗

Integrins: regulators of embryogenesis.

Integrins are heterodimeric transmembrane glycoproteins involved in cell-cell and cell-extracellular matrix adhesion. They also participate in cytoskeletal rearrangements, co-regulation of growth factor activities and activation of signal transductions. This review describes experimental approaches that have given new insights into the integrin functions during embryogenesis. Using anti-functional antibodies, peptide inhibitors of integrin-ligand interactions and genetic ablation of integrins results, this review will show that integrins are key molecules during early development of both invertebrates and vertebrates.

Animals↗

A key function for alphav containing integrins in mesodermal cell migration during Pleurodeles waltl gastrulation.

During cleavage of Pleurodeles waltl amphibian embryos, inner cells of the blastocoel roof (presumptive ectodermal and mesodermal cells) organize a fibrillar extracellular matrix (ECM) containing fibronectin on their basal surface by a beta1-integrin-dependent process. This matrix is used as a migratory substrate by mesodermal cells during gastrulation. While alpha5beta1 integrin is expressed on both ectodermal and mesodermal cell surface, we have shown previously that alphav containing integrins are essentially restricted to the surface of mesodermal cells (Alfandari, D., Whittaker, C. A., DeSimone, D. W., and Darribère, T., Dev. Biol. 170, 249-261, 1995). To investigate the function of alphav integrins during gastrulation, we have generated a function blocking antibody directed against the extracellular domain of the Pleurodeles integrin alphav subunit. The antibody did not prevent fibronectin fibril formation, whereas an antibody against the alpha5beta1 integrin did. When injected into the blastocoel, the antibody against integrin alphav subunit perturbed gastrulation and further development in a stage-dependent manner. Developmental defects were correlated to an abnormal positioning of the mesoderm layer. In vitro, the antibody blocked spreading of mesodermal cell to fibronectin or blastocoel roof ECM but not their attachment. In contrast, the antibody directed against the alpha5beta1 integrin inhibited both cell attachment and spreading to the same substrates. We propose that the alpha5beta1 integrin is required for fibronectin assembly into fibrils and mesodermal cell attachment to the blastocoel roof ECM, while the alphav containing integrins are necessary for cell spreading, and possibly migration, on this complex network.

Animals↗

Assessment of diazepam loading dose therapy of delirium tremens.

The efficacy of the diazepam loading dose method of treatment of delirium tremens was assessed in comparison with the traditional therapy. The experimental group and the control group comprised 51 and 45 patients respectively. The clinical institute withdrawal assessment for alcohol (CIWA-A) scale was applied to assess the intensity of the symptoms. Diazepam doses in the experimental group oscillated from 40 to 210 mg (mean 86.9 +/- 47.2 mg). The control group was receiving diazepam and other psychotropic drugs in divided doses. In the experimental group deliric symptoms were present from 2 to 24 h (mean 6.9 +/- 4.8 h), and in the control group from 2 to 123 h (mean 33.8 +/- 25.7 h). The results show a large efficacy of the loading dose method corresponding to substantial reduction of the psychosis duration (fivefold in comparison to the control group). The method proved to be safe, with no significant complications.

Adult↗

Analysis of complexity of EEG during sleep.

New multichannel descriptors of EEG activity: complexity (omega), total power (zeta) and generalized frequency (phi) were applied to whole night sleep analysis in 11 healthy subjects. The values of omega and phi decreased systematically from waking to slow wave sleep, and increased systematically in consecutive NREM-REM sleep cycles. The changes of zeta were opposite to omega and phi. These descriptors may be an alternative approach to the EEG sleep analysis.

Adult↗

Interhemispheric differences of sleep EEG complexity.

Complexity of EEG (omega), a global measure reflecting degree of spatial synchronization, was computed for whole night recordings of sleep EEG of 10 healthy volunteers, 9 males and 1 female (age 21-53) and 6 depressive patients, 5 males and 1 female (age 23-64). Sleep was scored visually in 20 s epochs, omega was calculated in 2.5 s segments and the median from 8 segments (20 s) was calculated. omega was calculated for the whole field of 21 electrodes and for the left and right hemisphere separately (2 x 8 electrodes). Measure of global power (sigma) and generalized frequency (phi) were also computed for the same data. In healthy subjects the complexity was higher over the right hemisphere during waking, and the difference shifted to higher complexity over the left hemisphere in slow wave sleep (F = 5.15, df1 = 4, df2 = 6856, P < 0.0005). The opposite trend was found in depressives (F = 10.51, df1 = 4, df2 = 3960, P < 0.0001).

Adult↗

Principles, main goals and methods of the nationwide program: "investigations on iodine deficiency and model of iodine prophylaxis in Poland".

The main reasons to start investigations on IDD in Poland as a nationwide project of the Ministry of Health and Welfare sponsored by the State Committee For Scientific Research and Foundation for Polish Science were: cessation of iodizing of kitchen salt in Poland in 1980, increase of the incidence of goitre in the population and hyperthyrotropinemia in newborns, results of the survey undertaken after Chernobyl disaster indicating an increase of goiter incidence (Nauman et al.) and results of the pilot study (Gutekunst, Gembicki, Kinalska and Rybakowa) indicating an increase of thyroid volume and diminishing of iodine excretion in urine of children in Kraków, Białystok ad Poznań regions. Therefore the main goals of the project were as follows: to evaluate IDD in Poland on the population basis, to map goiter incidence and iodine deficiency in geographic areas, to evaluate a voluntary model of iodine prophylaxis in Poland (20 mg of KI/kg of salt). The investigations were carried out in 19330 children (48.7% of boys and 51.3% for girls) in age group 6-13 years, attending 111 coeducational randomly selected schools from all the country. This number represents 0.35% of children subpopulation in the above age-groups. For practical purposes local coordinating centers at the relevant Departments of Endocrinology and Board of Coordinators were set up. The programme of survey included: filling the questionnaire by children's parents, thyroid palpation and classification according to WHO and ICCIDD criteria, thyroid volume determination by means of ultrasonograph Kontron Sigma 1 L with linear transducer 7.5 MHz, determination of iodine in casual morning urine sample using Sandell and Kalthoff method. Determination of iodine concentration in urine was performed in each case of goiter and in the same number of children without goiter. The results were segregated according to coordinating centers and according to 6 geographical areas of the country. The results were calculated according to the descriptive statistics using Student's test, Chi-square test F-test and Leven's test. The results segregated according to geographic areas were tested by means of analysis of variance using the linear model. The final results of the programme are presented in the next papers.

Adolescent↗

Goiter incidence and urinary iodine excretion in children of age group 6-13 years living in south-eastern Poland (Kraków coordinating center).

The study included 4103 school children attending randomly selected schools localized in towns and villages of 3 geographically distinct regions: mountainous, (Carpathian endemia), upland, lowland. The children were divided into four age-related groups. The incidence of goiter as detected by palpation was 38.1% in all the children studied, the value being similar in all three regions (38.1, 37.3 and 38.6%, respectively). Goiter incidence differs slightly among urban and rural children, amounting to 40.5 and 34.5%, respectively, in the two groups. In about 60% of children urinary iodine excretion was lower than 50 micrograms/l, while in about 30% it was normal. In about 10% of children studied urinary iodine excretion was lower than 20 micrograms/l. The results obtained indicate the occurrence among children of the studied region of goiter endemy of moderate degree. It was found that the percentage of children excreting more than 50 micrograms/l of urinary iodine was higher among those consuming iodized salt as compared to those consuming non-iodized salt. The first effects of resumption of common salt fortification with iodide in southern Poland can already be noted. There is, however, a need for optimization and steady control over this prophylactic action.

Adolescent↗

[Results of epidemiologic studies performed after the disaster in Czernobyl among the adult part of the population in the region of Krakow].

Epidemiologic studies following the Czernobyl accident were performed in region Kraków, including Kraków, Nowy Sacz and Kielce district. 1426 males and 2495 females were selected according to the random sample on the whole population of Kraków and Nowy Sacz, as well as in some selected areas in Swietokrzyski Mountains, and in Kielcecity. The aim of the study was to assess the results of the prophylaxis with Kalium iodine after the radiation and the incidence of the goiter in the population. It was stated, that 19.2% of the population in Kraków district, 16.9% in Nowy Sacz and 20% in Kielce received the prophylactic dosis of K.J. 80% took mainly the Lugol solution, between May, the 1st and 5th, 1986. Among 18 of person showing side effects like gastrointestinal disturbances, 16 were of female sex. Goiter incidence according to WHO classification was 50.7%, 67.3% and 49.9% in Kraków, Nowy Sacz and Kielce respectively. The difference between the incidence of goiter in males and females was 1:3. In women it was rather Ist and IInd degree of goiter, in men OB and Ist. Nodules of thyroid gland in the rural region of Kraków, Nowy Sacz and Kielce were seen in women in 10.8%, 1.7%, add 12.3% consecutively. Hormonal studies i.e T3, T4, TSH serum concentration showed normal results in all groups studied. TSH concentration was the highest in the group OB. The microsomal and antithyroglobulin antibodies level was the same independently on the prophylactic dosis of Lugol solution. The high incidence of thyroid diseases not related to the accident was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Electrophysiological mapping of sympathetic nuclei in the L2 and L3 segments of the spinal cord.

The spinal sympathetic preganglionic nuclei were mapped using antidromic field potential analysis during electrical stimulation of L2 and L3 white rami. The spinal sympathetic nuclei were localized respectively in L2 and L3 segments of the lumbar cord as a narrow strip along craniocaudal axis of the spinal cord. The caudal and of each preganglionic sympathetic nucleus was localized caudally to the corresponding dorsal root entry (DRE). The cranial end of the nucleus in different experiments was localized at different levels along the corresponding DRE or cranial to the corresponding DRE. We suggest that neurones which send axons to a single white ramus form an anatomically separate sympathetic preganglionic nucleus in the lumbar spinal cord within one segment.

Animals↗

Resolution of D-serine dehydratase by cysteine. An analytical treatment.

A general method is presented for analysis of the resolution of pyridoxal-P-requiring enzymes by carbonyl reagents. The method is useful for accurately determining the very small equilibrium constants (KP) which characterize the dissociation of cofactor from many pyridoxal-P-requiring enzymes. The analysis also establishes the minimum number and relative stabilities of distinct enzymic species involved in the resolution process. Analysis of the resolution of D-serine dehydratase by L-and D-cysteine resulted in the establishment of an enzyme bound thiazolidine derivative as an intermediate in the pathway for resolution. The over-all equilibrium constant (KR) for the reaction, D-serine dehydratase + cystein in equilibrium KR thiazolidine derivative +D-serine apodehydratase was determined. At pH 7.80, T/2 0.33, 25 degrees, KR equal to 1.08 times 10-minus 3. A value of 7.0 nM for the equilibrium constant for the dissociation of D-serine dehydratase to apoenzyme and free pyridoxal-P was determined from the ratio KR/KT, where KT is the equilibrium constant for the formation of a thiazolidine derivative from free pyridoxal-P and cysteine. An estimate of 14 nM for KP was also obtained from partial resolution of D-serine dehydratase by high dilution. The difficulties associated with this direct determination of KP from the dependence on the enzyme concentration of the activity of very dilute solutions of enzyme are discussed.

Cysteine↗

Separation and evaluation of the covalent and noncovalent interactions which contribute to the binding of pyridoxal 5'-phosphate to D-serine apodehydratase.

The equilibrium constant (KX) for the reaction D-serine dehydratase + pyridoxamine-P in equilibrium KX D-serine apodehydratase: pyridoxamine-P + pyridoxal-P was determined. At 25 degreees, pH 7.80, KX increases from 5.4 times 10-minus 5 to 21 times 10-minus 5 as T/2 is increased from 0.33 to 0.66. A value of 1.3 times 10-minus 4 M at 25 degrees, pH 7.80, T/2 0.33 for the equilibrium constant (KPMP) for dissociation of pyridoxamine-P from D-serine apodehydratase was determined from the ratio of the equilibrium constant for dissociation of pyridoxal-P from holoenzyme to KX. Pyridoxamine-P and the thiazolidine, formed from pyridoxal-P and cysteine, were found to have similar affinities for D-serine apodehydratase. Using the affinities of these derivatives as a measure of the noncovalent interactions between cofactor and protein, it was possible to estimate the contribution of the Schiff base linkage to the stability of the complex formed between pyridoxal-P and protein. The covalent Schiff base linkage in the holoenzyme was found to be no more stable than the Schiff base linkage formed between 6-aminocaproic acid and pyridoxal-P. The contribution of noncovalent interactions to the stability of the cofactor-protein complex was shown to be at least 20 to 40 times greater than the contribution of the covalent Schiff base linkage.

Chromatography, Gel↗