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Biomedical subjects

J Dvoráková

Publications and source records attributed to J Dvoráková.

At least 19 recordsLinked to original sources

Moderate hyperhomocysteinemia in patients treated for epilepsy.

Homocystein (Hcy) is regarded as a neuroexcitatory substance, which is therefore used as an epileptogenic agent in experimental epileptology. Experiments "in vivo" as well as "in vitro" revealed its relation to NMDA glutamate receptors, and its potential neurotoxicity. From the clinical aspect, hyperhomocysteinemia (HHcy), mostly as a marker of the risk factor in the vascular damage, was often studied in patients treated with antiepileptic drugs (AE). However, the neuroexcitatory influence of mild HHcy (up to 30 micromol/l) was rarely discussed. Out of a group of 123 adult patients on long-term conventional AE we analyzed 8 patients (7 men and one woman) with moderate to severe HHcy (30.7-109.0 micromol/l) retrospectively and 2-5 years after HHcy normalization. All of them suffered from partial and/or secondary generalized seizures accompanied by neuropsychological impairment depending on the aetiology of the disease. The patients were characterized by a concurrence of several factors: (1) All of them received conventional AEs inducing the cytochrome P 450 at the time HHcy was diagnosed. (2) Molecular-genetic tests showed enzymopathic impairment (methylentetrahydrofolate reductase-MTHFR mutation of the gene C677 T) also in all eight, homozygous in 7 cases and heterozygous in 1 case. (3) All patients were found to have a vitamin deficit or marginal values of at least one of the vitamins under study, especially folate and/or vitamin B6 and 812. With reference to clinical and EEG features, the potential neuroexcitatory influence of Hcy is discussed taking into account its effect on pathogenetic factors.

Adult↗

[Pharmacological aspects of Lyme borreliosis].

Clinical signs of Lyme boreliosis in humans are versatile and in their whole scope they finally affect the nervous system, heart, and joints. The therapeutic effect of antibiotics is maximal in the first acute stage of the disease when doxycycline and amoxiciline are administered. These antibiotics possess a comparable in vitro effect, tissue penetration, pharmacokinetics, and therapeutic effect. The treatment of disseminated infections in the second stage, such as neuroborreliosis, carditis, and iritis, is difficult and with relative success they are treated with large doses of penicillin G, or cefriaxon, and doxycycline. The treatment of the third stage of borreliosis aims at chronic inflammatory changes in the affected organs. Antibiotics, however, are successfully effective only in 50% of cases. Administration of antibiotics, such as tetracycline, cefuroxim, doxycycline, or large doses of penicillin is a long-term one, coming up to four weeks. A special therapeutic regimen is used in pregnant women and children.

Anti-Bacterial Agents↗

Levels of apolipoprotein A-II in cerebrospinal fluid in patients with neuroborreliosis are associated with lipophagocytosis.

Levels of most of the examined proteins in cerebrospinal fluid (CSF) of 107 patients with neuroborreliosis were associated with cytological findings, the status of hematoencephalic barrier as evaluated by Qalb (cerebrospinal fluid to serum quotient) and the intrathecal synthesis of immunoglobulins. Cytological findings consisted of normal cytology, or both oligocytosis and pleocytosis of monocytes or lymphocytes. The lipophagic elements were present in 20% of samples. Concentrations of apolipoproteins A-I and A-II in the CSF were correlated with the concentration of albumin without regard to the CSF cytology. The levels of apolipoprotein B were increased only in samples with lymphocytic pleocytosis and Qalb > 7.4. The presence of lipophages in the CSF was significantly associated with the CSF concentration of apolipoprotein A-II.

Adolescent↗

Formation of myo-inositol phosphates by Aspergillus niger 3-phytase.

Kinetics of phytate hydrolysis by Aspergillus niger phytase and correlation between the amount of released phosphate and creation of lower myo-inositol phosphates were investigated. Phytase was able to hydrolyze myo-inositol hexakis-, pentakis-, tetrakis-, and trisphosphates. Finally, about 56% of total phosphate were released and myo-inositol bisphosphate was detected as the end-product.

Aspergillus niger↗

[Homocysteinemia--its significance in gynecology and obstetrics].

OBJECTIVE: Metabolic study on plasmatic levels of homocysteine (Hcy) in healthy women during normal or pathological pregnancy accompanied with corresponding levels of Hcy in amniotic fluid and foetal sera. Increased levels of Hcy--hyperhomocysteinaemia is respected as an independent risk factor accelerating the early development of vessel damage and causing the neural tube defects (NTD). DESIGN: Basic study to get our own data about Hcy in Czech healthy and population at risk of pregnant and non-pregnant women. SETTING: Department of Obstetrics and Gynaecology, 1st Faculty of Medicine, Charles University, Prague. METHODS: Total homocysteine in plasma, amniotic fluid and foetal sera was estimated by chromatographic method with use of fluorescence detection. RESULTS: Normal homocysteine in preclimacteric healthy nonpregnant women is: 9.7 +/- 1.6 mumol/l with evident age-dependence. In healthy climacteric women are higher levels of Hcy (corresponding to the men values): 11.8 +/- 2.6 mumol/l. After use of hormonal contraceptives the plasmatic levels of Hcy decrease: 7.2 +/- 2.0 mumol/l. In physiological pregnancies Hcy reachs the lowest values: 4.4 +/- 1.7 mumol/l with any evident oscillations during pregnancy. In women in childbed period was Hcy 8.4 +/- 2.1 mumol/l observed. In pathological pregnanciesare its levels slightly elevated: 6.3 +/- 2.1 mumol/l, most evident in placental abruptions: 7.5 +/- 1.7 mumol/l. In pregnant women with susp. results of screening on M. Down only unsignificant increase of Hcy was observed: 6.12 +/- 2.4 mumol/l. In amnial fluids of healthy pregnant women are levels of Hcy are quite low: 4.1 +/- 1.2 mumol/l with any oscillations during pregnancy. In foetal sera of pregnancies at risk (NTD, susp., trisomy, inborn errors of metabolism): 3.6 +/- 1.4 mumol/l of Hcy was detected. The foetoplacental quotient for Hcy is 0.62. CONCLUSION: Average values for Hcy were established in physiological as well as in pathological pregnancies and till now only limited diagnostic significance has been observed. The hyperhomocysteinaemia mentioned in previous papers was not in NTD observed because our pregnant patients were regularly supplemented with all critical vitamins (folate, B6, B12).

Adolescent↗

Phytase: sources, preparation and exploitation.

This review deals with phytase (myo-inositol hexakisphosphate phosphohydrolase) and covers microbiological sources, phytase occurrence in plants and animals, its purification, physico-chemical and molecular properties. Protein engineering of phytase and potential enzyme applications are discussed.

6-Phytase↗

[Hyperhomocysteinemia. A risk factor for the development of vascular diseases not associated with lipid levels].

BACKGROUND: Elevated total homocysteine plasma levels are considered a significant factor of vascular damage. As they are encountered in more than half the patients with atherosclerotic vascular damage the importance as a lipid-dependent or lipid-independent risk factor in the promotion of pathophysiological processes is discussed. METHODS AND RESULTS: In a group of 100 healthy subjects and 529 patients with indication for an aortocoronary or peripheral arterial bypass and in patients from the lipid clinic the mutual relation between total plasma homocysteine levels and selected indicators of the lipid metabolism was investigated. The following results more obtained: for total cholesterol a correlation coefficient of r = 0.26, for HDL-cholesterol r = 0.20, for LDL-cholesterol r = 0.21, for triacylglycerols r = 0.29, apolipoprotein A-I r = 0.06, apolipoprotein B r = -0.12 and for Lp(a) r = -0.03. To ensure correct evaluation of the homocysteine levels simultaneously also folate levels were examined (correlation coefficient r = 0.28), vitamin B12 r = (0.03) and fibrinogen r = (0.09). CONCLUSIONS: The authors did not detect an unequovical relationship between the total homocysteine level and selected lipid indicators in any of the patient groups (p < 0.05).

Adult↗

NKR-P1A protein, an activating receptor of rat natural killer cells, binds to the chitobiose core of uncompletely glycosylated N-linked glycans, and to linear chitooligomers.

NKR-P1 represent a family of activating receptors in rodent natural killer cells related to C-type animal lectins. We identify here the elements involved in the reactivity of the major receptor of rat, NKR-P1A, with N-linked oligosaccharides of glycoproteins. Plate inhibition assays with isolated, structurally defined N-glycans as inhibitors of binding of NKR-P1A to GlcNAc16-BSA revealed that the removal of both the external sialic acids and the penultimate galactose residues resulted in attaining of significant inhibitory activities. Surprisingly, additional plate inhibition and glycoprotein overlay experiments brought evidence that the core chitobiose, depending on its substitution, can per se support the interaction with NKR-P1A. In a series of linear chitooligomers (n = 2-7), the inhibitory activities reached a maximum for the chitotetraose. The ability of NKR-P1 to recognize both the periphery and the core region of complex type oligosaccharides may define its dual specificity towards carbohydrate components of eukaryotic (e.g., tumor) cell surfaces, but also reflect an evolutionarily conserved reactivity with microbial saccharides important in immune recognition and signaling functions.

Animals↗

Characterization of phytase produced by Aspergillus niger.

The extracellular activity of Aspergillus niger phytase at the end of the growth phase was 132 nkat/mL in a laboratory bioreactor. The purified enzyme has molar mass approximately 100 kDa, pH optimum at 5.0, temperature optimum at 55 degrees C and high pH and temperature stability. The Km for dodecasodium phytate, calcium phytate and 4-nitrophenyl phosphate are 0.44, 0.45 and 1.38 mmol/L, respectively. The enzyme is noncompetively inhibited by inorganic monophosphate (Ki = 2.85 mmol/L) and by Cu2+, Zn2+, Hg2+, Sn2+, Cd2+ ions and strongly by F- ones; it is activated by Ca2+, Mg2+ and Mn2+ ions. The substrate specificity of phytase is broad with the highest affinity to calcium phytate.

6-Phytase↗

beta-Glucosylation of chitooligomers by galactosyltransferase.

Galactosyltransferase from bovine milk was found to be able to utilise UDP-Glc to transfer Glc onto GlcNAc and chitooligomers[-beta-GlcNAc-(1-->4)-]n, n = 2-4. beta-Glucosylated products were used in binding studies with NKR-P1A protein cloned from rat natural killer cells.

Acetylglucosamine↗

Lack of evidence for the interaction between renin-angiotensin-aldosterone system and endothelin in vivo.

Aim of the study was to reveal the possible factors regulating plasma endothelin (ET) levels in vivo in patients with essential hypertension (EH) by the simultaneous determination of plasma renin activity (PRA) and plasma aldosterone (ALD). In addition, the possible relationship between ET and circulating endothelial cells as a marker of endothelial damage was also investigated. The postural test revealed a significant increase of ET levels (26.7 +/- 9 vs 11.5 +/- 3 fmol/ml, p < 0.05) in the upright position. Captopril administration did not change plasma ET levels. No significant correlation was found between ET and PRA or ALD. Although a tendency to a positive correlation between ET and circulating endothelial cells (as the marker of endothelial perturbation) was found, it did not attain statistical significance. Our data do not support the suggestion that the renin-angiotensin-aldosterone system plays a major role in the regulation of ET secretion in vivo in EH. Postural stimulation of ET secretion may be caused by other factors than renin-angiotensin-aldosterone system.

Adult↗

Phytase from Aspergillus niger.

132 microorganisms, isolates from soil and decayed fruits, were tested for phytase production. All isolates intensively producing active extracellular phytase were of fungal origin. The most active fungal isolates with phytase activity were identified as Aspergillus niger. At the end of the growth phase, the extracellular phytase activity produced by A. niger strain 92 was 132 nkat/mL, with strain 89 it was 53 nkat/mL. In both strains the extracellular enzyme activity exhibited two marked activity optima at pH 1.8 and 5.0 and a temperature optimum at 55 degrees C.

6-Phytase↗

[Relation between levels of atrial natriuretic factor and circulating plasma volume].

The authors investigated in a group of 50 subjects the influence of changes in the volume of circulating plasma on the feedback regulation of plasmatic concentrations of the atrial natriuretic factor (ANF). They proved a fairly close direct correlation between the plasma concentration of ANF and the plasma volume in litres (r = 0.465, p less than 0.01) and when expressed in percent of body weight (r = 0.546, p less than 0.01). The rising concentration of ANF with the patients' age (r = 0.381, p less than 0.01) may be due to actual age conditioned changes or the more frequent incidence of pathological conditions in more advanced age groups, leading to an increase of the ANF plasma level. The results indicate that in addition to pressure changes and distension of the atria in the regulation of the plasma concentration of ANF also changes in the circulating plasma and blood volume participate which thus influence by a feedback mechanism the volume homeostasis.

Adult↗

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↗

[Is it possible to predict the development of Nelson's syndrome in Cushing's disease after bilateral adrenalectomy?].

A detailed analysis of clinical and laboratory findings in a group of 66 patients with Cushing's disease treated with bilateral adrenalectomy, out of whom 15 developed Nelson's syndrome, gave evidence that Nelson's syndrome mostly affects children and young patients compared to older persons. Bilateral adrenalectomy performed in patients aged over 40 years was never accompanied by Nelson's syndrome. Basal plasma ACTH values prior to adrenalectomy (30.9 +/- 4.53 pmol/l in the absence of Nelson's syndrome and 31.3 +/- 5.41 pmol/l in patients with Nelson's syndrome) as well as the degree of their suppressibility with 8 mg dexamethane (to 18.8 +/- 3.43 pmol/l in Nelson's syndrome and 19.0 +/- 3.44 pmol/l in patients without it) did not provide sufficient evidence for the prediction of later development of Nelson's syndrome. The same is true of the plasma cortisol concentrations. A tendency to a significant plasma ACTH increase after adrenalectomy within a 6-month period, and especially its lesser suppressibility raises a strong suspicion of an incipient development of Nelson's syndrome. These findings will have to be taken into account when deciding on the surgical treatment of Cushing's disease.

Adolescent↗

[The effect of clonidine on humoral factors in patients with arterial hypertension].

Clonidine, an agonist of central alpha-2-adrenergic receptors, reduced the peripheral sympathetic activity. With regard to the mutual pathophysiological relationship of blood pressure regulating mechanisms, the authors wanted to find out whether after clonidine administration, in addition to the known suppression of catecholamine levels (CA), also changes in the concentration of other pressor and depressor humoral substances will occur. They investigated therefore in 15 patients with essential hypertension (EH) and in three patients with pheochromocytoma the urinary excretion of free noradrenaline (NA), adrenaline (A) and dopamine (DA), the plasma renin activity (PRA), the aldosterone concentration (PAC) and atrial natriuretic factor (ANF) in plasma, using radioimmunoanalysis, always before and 24 hours after clonidine administration (Haemiton retardR) by the oral route. Its administration led in patients with EH to a decline of NA and DA. On the other hand, in pheochromocytoma their urinary excretion did not change in an unequivocal way, and when it declined, never normal NA and DA levels were reached. A excretion remained unaltered in both groups of patients. The drop of PRA after clonidine as a result of the drop of peripheral adrenergic activity was not associated with an expected parallel drop of PAC but by its rise. This effect can be explained by a reduction of the tonic inhibition of PAC output when the DA level declines. The rise of ANF after clonidine administration will be the subject of subsequent investigations. It cannot be ruled out that this effect is due to the direct action of clonidine on alpha receptors in the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗