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Biomedical subjects

A Szabó

Publications and source records attributed to A Szabó.

At least 19 recordsLinked to original sources

Mercury-stimulated histamine uptake and binding in cultured astroglial and cerebral endothelial cells.

The effects of mercuric compounds on histamine uptake and binding to uptake carrier in cultured rat astroglial and cerebral endothelial cells were investigated. Experimental results showed that mercuric compounds produced strong stimulation of glial and cerebroendothelial histamine uptake over a concentration range of 25-500 microM. The stimulated histamine uptake showed characteristics similar to those described for basal uptake in terms of sensitivity to inhibitory agents (e.g., impromidine) and the requirement of external Na+. Mercury-induced stimulation of histamine uptake could be abolished by sulfhydryl agents, dithiotreitol and cysteamine, indicating a complete reversal of, and not simply a protection from, the action of mercury. Basal and stimulated uptake of histamine represent bindings to uptake carrier with high and closely equal affinities but markedly higher capacities for stimulated uptake. In controls, the mean value of apparent KD (derived from saturation kinetics at equilibrium) was obtained as 26.7 +/- 3.9 nM for astroglial cells; and 100 microM mercuric chloride did not modify it significantly. In contrast, the apparent Bmax values differed markedly; found as 0.63 +/- 0.10 pmol/mg protein and 3.32 +/- 0.47 pmol/mg protein in the absence and the presence of 100 microM mercuric chloride respectively. For the cerebral endothelial cell line, RBE4, the apparent KD was calculated as 22.5 +/- 3.2 nM and was comparable to that obtained for astroglial cells in control and mercury-stimulated conditions. The apparent Bmax values were less, but markedly different in these conditions, obtained as 0.18 +/- 0.03 pmol/mg protein and 1.2 +/- 0.36 pmol/mg protein in the absence and the presence of mercuric ion respectively. In both cells, impromidine, the potent inhibitor of basal and stimulated histamine uptake, decreased the enhanced capacities of histamine binding (Bmax) (without affecting the dissociation constant, KD) in micromolar range, comparable to its inhibiting potency. Results confirmed that mercuric ion might enhance the binding capacity of histamine carrier and protein sulfhydryls might play a role in this effect. The observed stimulations by mercuric compounds suggest close similarities in the mechanism of histamine uptake and the structure of histamine carrier in astroglial and cerebral endothelial cells.

Animals

Possible relationship between histamine and nitric oxide release in the postischemic flow response following mesenteric ischemia of different durations.

During the postischemic flow response (PFR), vasodilator mediators such as nitric oxide (NO) and histamine are liberated, influencing the blood flow rate at the onset of reperfusion. The possible roles of these two mediators, and the relationship between their release, were examined during segmental intestinal ischemia of different durations and subsequent reperfusion in two series of anesthetized dogs. In series I (untreated ischemia), 15, 30, 60, and 120 min ischemia and 2 h reperfusion were studied. In series II, the same experimental protocol was repeated after pretreatment with the NO synthase inhibitor N-nitro-L-arginine (NNA, 10 mumol/kg, i.e., 2.19 mg/kg). Intramucosal pH (pHi), segmental blood flow and effluent histamine levels were measured, and segmental vascular resistance (SVR) and PFR volumes were calculated. The ischemic periods caused a considerable fall in pHi. Reperfusion resulted in an early return to normal pHi levels following a 15 or 30 min ischemia, but this process took longer after longer occlusions. In the later phase of reperfusion, SVR was elevated. The PFR volume increased in proportion to the duration of occlusion, except after the 120 min ischemia. At the onset of reperfusion, peak histamine levels rose in parallel with the duration of ischemia. During reperfusion, a prolonged decrease in pHi, an increase in SVR, and a reduction in PFR volume, with no significant histamine level elevation, were observed in the NNA-treated groups. This study indicates that both NO and histamine take part in the PFR in the canine small intestine. Inhibition of NO synthesis prevents the postischemic release of histamine.

Animals

Molecular genetic studies in monogenic and polygenic human diseases.

The main goal of this study was to determine and characterise the types of mutations in two monogenic human disorders: cystic fibrosis (CF) and Duchenne/Becker muscular dystrophy (DMD, BMD) and the susceptibility allele frequency in a polygenic disease: type I insulin-dependent diabetes mellitus (IDDM). After analysing 220 chromosomes for mutations in the CF (Cystic Fibrosis Transmembrane Conductance Regulator = CFTR) gene, delta F508 mutation was most abundant (41%) and out of the non-delta F508 CF mutations 5% was identified as G542X, G551D, R553X, N1303K and W1282X. The CF haplotype analysis by using linked markers to the CFTR gene revealed that the CF "B" haplotype occurred in 66.7% of patients, and this haplotype was 57.2% in patients carrying the delta F508 mutation. Prenatal genetic diagnosis for CF was performed in 10 fetuses: 3 were affected, 6 were carriers, and 1 without any CF mutation. Fifty % of 66 patients with DMB/BMD muscular dystrophy had one or more exon deletions in the dystrophin gene. Eighty-five % of the deletions occurred at the 3' and 15% at the 5' end of the gene. Out of the three prenatal diagnosis in one case DMD was substantiated. Thirty-six % of 50 patients with IDDM possessed four, 44% three and 20% two susceptibility markers in the HLA-DQA1, -DQB1 region. The onset of the disease correlated with the number of susceptibility alleles.

Alleles

Cardiovascular effects produced by R-(+)-8-hydroxy-2-(di-n-propylamino) tetralin in the preoptic area of conscious rats.

Experiments were designed to test the hypothesis that activation of forebrain 5-HT1A receptors elicits cardiovascular responses. The microinjection of R-(+)-8-hydroxy-2-(di-n-propylamino) tetralin [(+)-8-OH-DPAT], a selective 5-HT1A receptor agonist, in the preoptic area of conscious rats increased blood pressure and heart rate at doses of 0.2-20 nmol; lower doses (0.002 and 0.02 nmol) were ineffective. The concomitant administration of methiothepin, a non-selective 5-HT receptor antagonist, into the preoptic area attenuated the responses. In addition, the tachycardia elicited by (+)-8-OH-DPAT was abolished by the peripheral beta-adrenoceptor antagonist sotalol, but not by atropine methyl nitrate. Finally, the tachycardia, but not the hypertension, was also produced by (+)-8-OH-DPAT in urethane-anesthetized rats. These results suggest that activation of 5-HT1A receptors in the preoptic area or an adjacent region of the forebrain produces: (1) an increase in heart rate consistent with sympathoadrenal activation; and (2) an increase in blood pressure which might be the result of sympathoexcitation or secondary to behavioral arousal.

8-Hydroxy-2-(di-n-propylamino)tetralin

[Neonatal primary hyperparathyroidism].

The authors report on a case of severe primary hyperparathyroidism with clinical signs from birth. The boy was admitted because of poor somatomental development, hypotony, hepatosplenomegaly and osseous abnormalities, resembling those of rachitis. Laboratory data showed the typical findings of primary hyperparathyroidism. The authors performed parathyroidectomy with simultaneous heterotopic parathyroid tissue autotransplantation. Histology revealed parathyroid chief cell hyperplasia. Because of the hypercalcaemia and clinical signs persisting after the operation they removed the parathyroid autografts. Since this later was ineffective they performed a left sided neck dissection on the side of the excessive parathormone production. The child became hypocalcaemic necessitating calcium and vitamin D administration. He is now 17 months after the last operation. His somatomental development is accelerated. In connection with the case the authors surveyed the literature of this rare entity.

Humans

[Normal values of calcium and oxalate excretion in children].

Aim of the study was to establish normal values for calcium/creatinine (Ca/cr) and oxalate/creatinine (Ox/cr) ratio in infants and children. Urine probes of 416 healthy children (25 infants aged 1-7 days and 391 children aged 1 month-14.5 years) were analysed. Oxalate was measured by ion-chromatography. Urinary Ca2+/cr was normally distributed, Ox/cr had log-normal distribution. Ca/cr was the lowest in the first days of life, the highest between 7 month-1.5 years (mean +/- SD = 0.39 +/- 0.28 mmol/mmol), a slight decrease could be observed until 14 years (0.34 +/- 0.18). The highest Ox/cr values were measured during the first month of life (geometric mean/range/ = 133 /61-280 mmol/mmol/), followed by gradual decrease until 14 years (25/6-73/). The measurement of Ca2+/cr and Ox/cr in first morning urine samples is suitable for screening of hypercalciuria and hyperoxaluria. The interpretation of the values requires age specific reference values. Both calcium and oxalate determinations should be the part of the evaluation of patients with hematuria, hypercalciuria or nephrolithiasis.

Adolescent

A Raman study of the time variability for the A-to-B transition in wet-spun films of calf-thymus DNA.

The time evolution of the A-to-B transition has been monitored by Raman spectroscopy and found to vary significantly for different samples. Though all samples were prepared in the identical fashion, some samples completed the transition on the time scale of several hours while other samples took days. The shortest time required for the A conformation to disappear was about 2 hours, as determined by the disappearance of the A-form Raman band at 807 cm-1. For these fastest transforming samples, the B-form Raman band at 835 cm-1 was clearly evident after about 5 hours. These data are consistent with the hypothesis that the A conformation of DNA is stabilized by intermolecular interactions.

Animals

Abnormal expression and regulation of vitamin D receptor in experimental uremia.

The low concentration of the biologically active metabolite of vitamin D, namely 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), is critical to the pathogenesis of secondary hyperparathyroidism in chronic renal failure. The actions of 1,25(OH)2D3 are mediated through binding to a cellular receptor protein, the vitamin D receptor (VDR). In order to further investigate expression and regulation of VDR in uremia, we measured specific [3H]-1,25(OH)2D3 binding capacity and VDR mRNA concentration in intestinal mucosa and in parathyroid glands of subtotally nephrectomized rats (Nx) and compared Nx to sham-operated rats with normal kidney function (Intact). Intestinal [3H]-1,25(OH)2D3 binding capacity in short-term Nx (6-10 days after nephrectomy) was 663 +/- 114 fmol/mg protein; it was 517 +/- 34 in Intact (p = 0.06, n = 6 experiments). Intestinal VDR mRNA concentration was comparable between Nx and Intact. Specific 1,25(OH)2D3 binding capacity in parathyroid glands was higher in Nx (195 +/- 9 fmol/mg protein) than in Intact (116 +/- 14 fmol/mg protein, n = 5, p < 0.05). The affinity of the VDR for 1,25(OH)2D3 (KD) did not change in Nx. The 1,25(OH)2D3 binding capacity in intestinal mucosa of more long-term uremic animals (14-16 weeks after subtotal Nx) was 519 +/- 32 fmol/mg protein versus 349 +/- 31 in Intact (n = 3, p < 0.01). Parathyroid VDR was 171 +/- 9 fmol/mg protein in long-term Nx and 125 +/- 3 in Intact (p < 0.01). These results were confirmed when 1,25(OH)2D3 binding capacity in uremic rats with hereditary polycystic kidney disease was compared to control rats with normal kidney function (757 +/- 54 fmol/mg protein versus 495 +/- 59 in intestinal mucosa, p < 0.05; 273 +/- 48 versus 104 +/- 27 in parathyroid glands, p < 0.05). In parallel to changes in intestinal 1,25(OH)2D3 binding capacity, 1,25(OH)2D3-mediated stimulation of intestinal 25(OH)D3-24-hydroxylase activity was significantly higher in long-term subtotally Nx (1.43 +/- 0.06 pmol 24,25-dihydroxyvitamin D3/mg protein) than in sham-operated normal rats (1.04 +/- 0.10, p < 0.05). Administration of 1,25(OH)2D3 to sham-operated normal rats resulted in an increase of 1,25(OH)2D3 binding capacity by 20-40% in intestinal mucosa and by 40-50% in parathyroid glands. In contrast, 1,25(OH)2D3 caused down-regulation of mean 1,25(OH)2D3 binding capacity in short-term Nx by 38% in intestinal mucosa (p < 0.01) and by 43% in parathyroid glands (p < 0.01). In long-term Nx, mean 1,25(OH)2D3 binding capacity was reduced by 20% in intestinal mucosa (p < 0.05) and by 22% in parathyroid glands (p < 0.01). After prolonged exposure to 1,25(OH)2D3 for 6 weeks, intestinal 1,25(OH)2D3 binding capacity was markedly down-regulated in uremic rats (43% versus vehicle-treated animals p < 0.05). Taken together, our results provide evidence for abnormal expression and regulation of VDR in experimental uremia. This may be relevant for responsiveness to 1,25(OH)2D3 in renal insufficiency.

Animals

[Somatostatin plasma level in patients with liver cirrhosis].

The significance of changes in plasma somatostatin level at patients with vascularly decompensated liver cirrhosis was investigated. The plasma level of somatostatin, glucagon, gastrin and blood glucose concentration were determined under basal condition and after testmeal in patients with vasculary decompensated cirrhosis, in cirrhotic-patients without ascites formation and in control subjects. The basaline levels and the postprandial increases of plasma somatostatin concentrations were significantly lower in cirrhotic patients with ascites, compared to the other two groups. The glucagon concentrations--both the basaline and the postprandial--were significantly higher in the cirrhotic patients-groups, compared to the controls. The gastrin and blood glucose levels were not different in the three groups. The decrease in plasma somatostatin concentration present in cirrhosis associated with ascites represents a secondary phenomena, and suggest that endogen somatostatin plays a role in maintaining body fluid homeostasis.

Adult

Plasma amino acid concentration under human growth hormone treatment in uremic children.

The plasma amino acid concentrations were investigated before and after 3 and 30 months of human recombinant growth hormone treatment in 7 children with chronic renal failure. The concentrations of amino acids in plasma showed characteristic changes (pretreatment vs. after 3 and 30 months of treatment): Lys 113 +/- 33 vs. 162 +/- 27 and 109 +/- 38 mumol/l, Met 21 +/- 8 vs. 31 +/- 4 and 16 +/- 5, Thr 105 +/- 23 vs. 148 +/- 60 and 118 +/- 30, Ala 455 +/- 109 vs. 536 +/- 93 and 314 +/- 60, Gln 298 +/- 66 vs. 277 +/- 52 and 544 +/- 65, Glu 168 +/- 46 vs. 209 +/- 57 and 96 +/- 24, Gly 345 +/- 137 vs. 479 +/- 169 and 342 +/- 95, Pro 378 +/- 148 vs. 422 +/- 28 and 527 +/- 229, OH-Pro 33 +/- 17 vs. 105 +/- 23 and 97 +/- 35, Se 133 +/- 39 vs. 178 +/- 55 and 131 +/- 12 mumol/l. Long-term treatment with human recombinant growth hormone normalized plasma alanine, glutamine, and glutamic acid levels, increased the OH-Pro concentration, and did not alter the amino acid ratios of Gly/Val, Phe/Tyr, Ser/Gly, and Asn/Asp, but the Gln/Glu ratio approached the normal value.

Amino Acids

Blood pressure and heart rate reactivity to mental strain in adolescent judo athletes.

This exploratory investigation examined the association between maximal aerobic power (VO2max) and blood pressure (BP) and heart rate (HR) reactivity to mental challenge. Adolescent male judo athletes (n = 20) performed a 2-min mental arithmetic. Heart rate was recorded before, during, and after the arithmetic, and BP was recorded before and after the mental challenge. Blood pressure in the immediate stress-recovery period was not related to VO2max, but subjects having a higher maximal aerobic power showed faster HR recovery from mental stress than those having a lower VO2max. Subjects who showed earlier peak HR responses, during the stress episode, demonstrated lower average HR reactivity than subjects who attained the maximal HR response later in the stress period. The relationship between the interval to reach peak HR and the magnitude of reactivity deserves further attention. However, at present these findings should be viewed as tentative because of the uniqueness and size of the sample.

Adolescent

Role of histamine in the intestinal flow response following mesenteric ischemia.

Sudden reperfusion of the gut following prolonged ischemia can itself have more deleterious consequences than the ischemia alone. Studies of vasodilator factors influencing the increased flow on reperfusion are therefore of importance. In the present study, a possible role of histamine in the postischemic flow response was examined after a period of total segmental ischemia. The artery supplying the terminal ileum was occluded in anesthetized dogs. Ischemia of 30 min duration was followed by a 30 min reperfusion period (control postischemic flow response), and the arterial blood flow to the segment was measured. After the control postischemic flow response, one of the following drugs was administered intravenously: histamine H1-or H2-blockers (tripelennamine, .5 mg/kg, cimetidine, 10 mg/kg, ranitidine, 2 mg/kg), cromolyn (a mast cell stabilizer, 25 mg/kg), and aminoguanidine (a diamine oxidase blocker, 50 mg/kg). The 30 min ischemia-30 min reperfusion cycle was then repeated (test postischemic flow response). A 30 min mesenteric ischemia-reperfusion period is reproducible once without a significant change in its hemodynamic parameters. The duration and volume of the postischemic flow response were significantly decreased by cimetidine, ranitidine, or cromolyn, and were increased by aminoguanidine. Tripelennamine did not affect the postischemic vasodilator response. At the onset of reperfusion, a release of endogenous histamine occurs from the gut, originating mainly from mast cells. It is proposed that histamine participates in the postischemic flow response through the H2-receptors.

Animals

Sympathetic-adrenergic activity and acid-base regulation under acute physical stress in type I (insulin-dependent) diabetic children.

To evaluate the efficacy of the acute-physical-stress response, plasma catecholamine and lactate levels, serum electrolytes, fructosamine, blood glucose and acid-base status were measured in insulin-dependent diabetes mellitus (IDDM) children and the data compared to those of healthy controls. Four groups were studied: group 1, healthy controls; group 2, newly diagnosed diabetic patients with an IDDM duration of 2-4 weeks; group 3, with an IDDM duration of 5-7 years; group 4, with an IDDM duration of 10-13 years. According to their fructosamine levels, IDDM children were in a well-controlled metabolic state. The physical stress was induced by 1.5-1.7 W/kg/10 min bicycle ergometer determined by a target pulse rate of 170/min. IDDM children exhibited pronounced lactic acidosis under stress (pH: group 2, 7.27 +/- 0.07; group 3, 7.28 +/- 0.05; group 4, 7.20 +/- 0.04, vs. group 1; 7.34 +/- 0.03). Baseline plasma norepinephrine and epinephrine levels showed a significant decrease parallel to the duration of IDDM. Stress induced an increase in the concentration of norepinephrine in each group, but the elevation was significantly higher in the IDDM children versus the controls. A significant negative correlation was found between pH and maximal plasma norepinephrine levels (y = 7.3-0.006x, r = -0.46, p < 0.02). Stress resulted in blood glucose elevation in 13 patients regardless of their pre-exercise blood glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium

Optical third harmonic generation study of the hydration of DNA films.

Optical third harmonic generation (THG) has been observed for the first time from DNA films. The THG signal is observed from NaDNA films exposed to relative humidities (RHs) between 0% and 98%. A strong enhancement (approximately 5x) of the THG signal from NaDNA is observed at 84% RH; no enhancement is observed for RbDNA. The most likely mechanism for such an enhancement is an increased coherence length. A model calculation using estimates of the refractive indices at both the fundamental and third harmonic frequencies supports this interpretation. The observed THG signal has the same polarization as the incident (fundamental) light. For the A conformation, the THG signal polarized perpendicular to the helical axis is approximately twice as strong as the signal polarized parallel to the helical axis. No such anisotropy is observed for either the disordered conformation (below about 50% RH) or the B conformation (above 92% RH).

Biophysics

Aerobic fitness does not influence directly heart rate reactivity to mental stress.

Thirty-seven aerobically high and low fit male and female university students, selected on the basis of estimated aerobic capacity, completed a set of hard as well as a set of easy mental arithmetic tasks for 90 seconds in a counterbalanced order with a 10 min rest period between the tasks. Heart rate (HR) reactivity to either task was independent of aerobic fitness level. Although subjectively rated as more challenging, HR responses to the hard arithmetic task were not greater than that seen to the easy task. These results do not support the conjecture that aerobic fitness level may mediate HR response to acute mental challenge. The overall implications of these results are discussed in relation to the literature concerning aerobic fitness and mental stress.

Adult

The effect of pesticides on carp (Cyprinus carpio L). Acetylcholinesterase and its biochemical characterization.

The activity and molecular forms of acetylcholinesterase (AChE) were characterized in tissues of the carp (Cyprinus carpio). Tissue AChE activity was determined in response to specific inhibitors (ethopropazine, BW 284 C51) or pesticides (CuSO4, paraquat (PQ), methidathion (MD)). The highest AChE activity was found in the serum (878 +/- 100 U/liter), followed by the brain (113 +/- 12 U/liter), heart (89 +/- 6 U/liter), and trunk muscle (35 +/- 5 U/liter). Experiments with specific choline esterase inhibitors revealed a very low amount of pseudocholinesterase in all tissues studied. The ratio of the membrane-bound to the cytoplasmic-free AChE molecular forms was increased in the order of brain, trunk muscle, and heart. In sera of fish treated with MD (2 ppm) there was an 80% inhibition of AChE lasting for 2 weeks. Treatment with CuSO4 or PQ (both 5 ppm) led to a 50% decrease in the serum AChE activity followed by a transient increase over the control level. After 2 weeks of chronic treatment, AChE activity in fish exposed to CuSO4 returned to the control level, whereas in fish treated with PQ an elevated level (130% when compared to the control level) of enzyme activity was found. Our present experimental data indicate that pesticides occurring in natural waters not only inhibit AChE activity in fish but may influence the resynthesis of the enzyme as well.

Acetylcholinesterase