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Biomedical subjects

E Molnár

Publications and source records attributed to E Molnár.

At least 19 recordsLinked to original sources

[Serum bone marker measurements in bone metabolism disorders associated with inflammatory bowel diseases].

Patients with inflammatory bowel disease (IBD) have decreased bone mineral density (BMD), which is usually much more remarkable in patients with Crohn's disease (CD) than those with ulcerative colitis (UC). The aim of the present study was to investigate the usefulness of serum beta-Crosslaps (bCL) and osteocalcin (OC) determinations to assess bone metabolism in patients with IBD. Forty-nine patients with IBD (23 UC, 26 CD) and 46 healthy controls were studied. Serum bCL and OC were measured by Elecsys immunoassay. Compared to controls (0.275 +/- 0.14 ng/ml) the mean bCL concentration was significantly higher in the CD (mean = 0.489 +/- 0.25 ng/ml; p < 0.001) and UC groups (mean = 0.439 +/- 0.3 ng/ml; p < 0.01). The mean OC concentration was significantly higher in the CD group (28.52 +/- 14.75 ng/ml) than in controls (21.42 +/- 7.43 ng/ml) but OC level was not significantly increased in the UC group (24.89 +/- 15.08 ng/ml). There was no significant difference in bCL or OC concentrations between the CD and UC groups. These results indicate that the accelerated bone resorption is not associated with increased bone formation in patients with IBD. These two marker of the bone metabolism could be a good laboratory parameter of bone pathology in patients with IBD, especially in CD.

Adult↗

Teratogenicity testing of BI 58 EC (38% dimethoate) in chicken embryos with special respect to degradation of the active ingredient.

The insecticide formulation BI 58 EC was tested for teratogenicity in chicken embryos, with particular reference to degradation of the active ingredient (dimethoate) after the treatment of embryonated eggs. The pesticide was diluted in water to a concentration level of 0.8%, and the emulsion was injected into the air space in a volume of 0.1 ml/egg, or hen's eggs were treated by the immersion technique. Residues of dimethoate were measured in the samples on days, 13, 15 and 19 of the incubation of chicken embryos, and morphological examinations were performed simultaneously. Analytical chemistry data indicated a slower degradation of dimethoate in embryos after the immersion of eggs, and cyllosis was remarkable in this group among the sporadic developmental anomalies. The liver tissues of both treated groups exhibited severe fatty infiltration.

Abnormalities, Drug-Induced↗

Interaction of Dithane M-45 (mancozeb) and lead acetate during a teratogenicity test in rats.

The teratogenic effects of lead acetate (Trial 1) and the possible teratogenic effect of this compound administered in combination with a fungicide containing 80% mancozeb (Trial 2) were studied in rats. The test substances were administered by gavage on Days 6-15 of gestation. In Trial 1, five groups were treated with lead acetate administered at doses of 0.1, 0.5, 1.0, 10.0 and 1000.0 mg/kg body weight (bwkg), respectively. In Trial 2, lead acetate was applied at doses of 0.1, 10.0 and 1000.0 mg/bwkg, respectively. In the latter case the dose of the pesticide was 750 mg/bwkg in all treated groups. Lead acetate was not teratogenic after a single administration. Combined administration of lead acetate and mancozeb gave rise to the following toxic effects: average maternal weight decreased during pregnancy, the ratio of live fetuses decreased after the two lowest doses, and fetal mortality increased in the lowest and in the highest dose groups. The ratio of fetal resorption was higher in all the treated groups than in the control group. A significant decrease occurred in average fetal and placental weight in each treated group as compared to the control. Maternal toxicity was expressed in paralysis of the hindlimbs in the two lowest dose groups. Maternal mortality was between 16.7 and 23.3% at the three dose levels. Phocomelia and hernia cerebri occurred as characteristic fetal developmental anomalies in all the treated groups. It is concluded that the joint administration of lead acetate and a mancozeb-containing fungicide can cause maternal toxicity, embryotoxicity and characteristic teratogenic effects.

Abnormalities, Drug-Induced↗

Effect of immersion fluid temperature on the chicken embryo in teratogenicity tests: short communication.

The influence of immersion fluid temperature on the development of the chicken embryo was studied on the day most commonly used for treating incubated eggs in teratological trials. Embryonated eggs were immersed in tap water for 30 min on the 12th day of incubation at 22-25 degrees C or at incubation temperature without a waiting time or after 30 min. The incubation was then continued and the eggs were processed on day 19 of the incubation period. Treatment of eggs at 22-25 degrees C caused a significant increase in embryonic mortality, while the 30-min waiting time did not exert an influence on embryogenesis.

Animals↗

Differential changes in the subcellular distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate and N-methyl-D-aspartate receptors in neonate and adult rat cortex.

We compared the distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors and their individual subunits in synaptosomal and microsomal fractions prepared from 2-day-old (P2) and adult rat cortex. In P2 cortex more [3H]-(S)-fluorowillardiine ([3H]FW) binding to AMPA receptors was in the intracellular microsomal fraction than in the synaptosomal fraction whereas in adult rats the reverse was observed. Immunoblots with GluR1, GluR2/3, GluR4 and pan-AMPA antibodies showed the same profile. In contrast, the majority of [3H]MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor and NR1 subunit immunoreactivity was present in the synaptosomal fraction at both developmental time points. These results suggest a developmental rearrangement of the distribution of AMPA receptors within neurons, a process which is likely to be important in synaptic stabilization and plasticity.

Aging↗

Cyclosporin and sulfasalazine combination in the treatment of early rheumatoid arthritis.

The aim of the study was to assess the efficacy of a new formulation of cyclosporin-A (CyA) and sulfasalazine (SASP) combination treatment in preventing disability and reducing inflammatory disease activity in patients with early rheumatoid arthritis, as well as to assess the tolerability, safety, and suitability for long-term treatment. Forty five patients with early, active rheumatoid arthritis, (RA) were treated with CyA and SASP combination therapy for 12 months. The patients were evaluated by disease activity and radiologic measurements. The combined CyA and SASP therapy seems to be effective. Disease activity parameters improved within 3 months. The individual treatment response rate according to EULAR response criteria was 78% after a one year treatment period. Five patients were withdrawn due to gastrointestinal side effect and two patients because of lack of efficacy. CyA and SASP combination treatment seems to be effective in early severe RA, and with careful monitoring, side effects can be kept under control.

Adult↗

Model field study of Sumithion 50 EC and Fusilade S on pheasants.

Toxicological studies on wild animals play an important role in the ecotoxicological examination of pesticides. The applied model tests enable the assessment of toxicological consequences with particular regard to the life and nutrition of wild animals in the ploughed field among plants treated with pesticides. The application of different pesticide formulations on plough-land may pose a simultaneous chemical burden to wild birds. In this model study, manifestations of the interaction between an insecticide and a herbicide were studied in pheasants. The birds were placed on lucerne in cages (48 m2) and sprayed once. The applied doses were: Sumithion 50 EC 1 litre/ha + Fusilade S 6 litres/ha (practical doses) and Sumithion 50 EC 5 litres/ha + Fusilade S 30 litres/ha. The analytically determined pesticide concentration of the lucerne was taken as a basis in the further treatment of fodder. The fodder of pheasants contained the following chemicals: 85 mg/kg Sumithion 50 EC + 510 mg/kg Fusilade S and 425 mg/kg Sumithion 50 EC + 2250 mg/kg Fusilade S. Sporadic deaths observed among the pheasants were of traumatic origin and not due to a toxic effect. The decrease of body weight was significant only at the higher dose levels. Acetylcholinesterase (AChE) activity of the blood decreased significantly in both dose groups. On the basis of the results obtained it can be established that at the dose level used in the practice the pesticides studied do not give rise to a toxic interaction in pheasants.

Acetylcholinesterase↗

Embryonic toxicity of insecticide Sumithion 50 EC and herbicide Fusilade S in pheasants after individual or combined administration.

The purpose of this work was to determine the individual and combined effects of insecticide Sumithion 50 EC (50% fenitrothion) and herbicide Fusilade S (12.5% fluazifop-P-butyl) on the development of pheasant embryos. Eggs were treated by injection of various concentrations of pesticides into the air space on day 12 of incubation. Pathological examination of embryos was carried out on day 23 of the hatching period. Mortality rate, body weight data and morphological alterations were evaluated after the macroscopic examination. The skeletal staining method was used to detect deformities. The two pesticides used in combination moderated the toxic/teratogenic effects of individual treatment.

Animals↗

Regional distribution and developmental changes of GluR1-flop protein revealed by monoclonal antibody in rat brain.

From immunizations of mice with a glutathione S-transferase fusion protein containing residues 724-781 of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR1-flop, two monoclonal antibodies (mAbs) were developed that differed widely in their ranges of specificity. In immunocytochemical and immunoblotting assays performed on COS-7 cells transfected with one of the eight GluR1-4-flip/flop forms, mAb 19B10 recognized all eight forms, whereas mAb 8E11 was specific for GluR1-flop. By means of synthetic peptides, the epitopes were determined to be NKWWYDKG (GluR1-flop760-767) for mAb 19B10 but GSALRNPVN (GluR1-flop740-748) plus a partial epitope, QGLL (GluR1-flop757-760), for mAb 8E11. Further analysis on synthetic peptides pointed to a potential cross-reactivity of mAb 8E11 with GluR2-4-flop variants that lacked editing at the R/G site. The contribution of such cross-reactivities in histoblot labeling patterns on adult rat brain material, however, was judged to be negligible. Histoblot patterns with mAb 8E11 were dominated by strong immunoreactivity in CA1 strata radiatum and oriens and in the dentate molecular layer, whereas the CA3 region was virtually free of labeling. This pattern and those observed at different stages of postnatal development were generally similar to regional distribution patterns previously reported in the literature for GluR1-flop transcripts. Key Words: Glutamate receptors-AMPA receptor subunits-Alternative splicing-Developmentally regulated expression-R/G site.

Alternative Splicing↗

[Molecular biological studies on patients with nephrogenic diabetes insipidus].

Nephrogenic diabetes insipidus is a rare, mostly X-linked recessive disorder characterised by renal tubular resistance to the antidiuretic effect of arginine vasopressin. The gene responsible for the X-linked nephrogenic diabetes insipidus, the G-protein-coupled vasopressin V2-receptor, has been localised on the Xq28 region. In this study four patients were investigated with molecular genetic methods. Diagnosis was based on clinical symptoms and lack of increase of urinary osmolality after administration of the arginine vasopressin, or the synthetic vasopressin analogue DDAVP. Three different mutations (C112R, N317K, W323S) were found in three patients, while no mutation was detected in the fourth patient. Since earlier histiocytosis X has been diagnosed in this patient, this patient has probably central diabetes insipidus. Although the main symptoms of the disease can be found in all patients, there are significant differences in the seriousness of the symptoms as well as in some other symptoms. The explanations might be the different mutations in the V2-receptor gene and the various other genetic and environmental factors; these findings provide further evidence that X-linked nephrogen diabetes insipidus results from defects in the V2-receptor gene.

Diabetes Insipidus, Nephrogenic↗

Eradication of brucellosis from a cattle herd in the Amazonian region (short communication).

The authors intend to elaborate a brucellosis eradication program which could be used in the Amazonian region, an area characterised by extremely extensive animal husbandry practices. Under such conditions, eradication by selection is the only feasible approach. Brucellosis has been successfully eradicated from a herd with 22.1% prevalence of infection by two serological surveys using an indirect ELISA and the complement fixation test.

Agglutination Tests↗

Value of different serological tests in the diagnosis of bovine brucellosis in the Amazonian region.

The high prevalence of brucellosis is one of the most serious animal health problems affecting cattle and buffalo herds of the Amazonian region. Modern diagnostic methods are not used or not even known, and thus test results are not available in that region. Therefore, in this study a total of 878 selected sera were subjected to comparative examination by five different serological tests (buffered plate agglutination test, tube agglutination test, complement fixation test, indirect ELISA, competitive ELISA). Indirect ELISA gave the highest number of positive results, except in samples derived from the Marajó island, for which the competitive ELISA proved to be the most sensitive. The sensitivity of the classical tests (agglutination, complement fixation) was markedly lower than that of the two ELISAs. After vaccination of 2-month-old heifer calves with the B19 vaccine, all tests showed a 50-60% seropositivity, which disappeared within four months.

Agglutination Tests↗

[Systemic mastocytosis].

The systemic mastocytosis is a rare disorder, however, the authors recently diagnosed two cases causing diagnostic problems. The diagnosis was proved by bone marrow biopsy in both patients. The authors review the diagnostic pathway considering the pitfalls. According to their conclusion, the most important factor in the diagnosis of systemic mastocytosis is to think of the possibility of systemic mastocytosis.

Aged↗

Isoforms of endoplasmic reticulum Ca(2+)-ATPase are differentially expressed in normal and diabetic islets of Langerhans.

Glucose-dependent sequestration of Ca2+ into endoplasmic reticulum and its subsequent release play an important role in the control of intracellular Ca2+ concentration, which regulates insulin secretion in pancreatic beta-cells. The active uptake of cytosolic Ca2+ into endoplasmic reticulum is mediated by sarco-(endo)plasmic reticulum Ca(2+)-ATPases (SERCAs). We found, using RT-PCR with isoform-specific primers, that SERCA 2 and SERCA 3 mRNAs are co-expressed in human and rat islets of Langerhans and in the RINm5F beta-cell line. Immunochemical analysis also revealed the existence of two SERCA proteins with molecular masses of 110 and 115 kDa in beta-cell membranes. The 115 kDa protein was identified as SERCA 2b by its reaction with an isoform-specific antibody and the 110 kDa protein most probably corresponds to SERCA 3. The presence of two functionally different SERCA isoforms raises the possibility that they are located in distinct Ca2+ stores. There is evidence that altered Ca2+ handling in the beta-cell may contribute to the decreased insulin secretion seen in non-insulin dependent diabetes mellitus (NIDDM). We therefore investigated SERCA 2 and SERCA 3 mRNA expression by quantitative RT-PCR in islets prepared from Goto-Kakizaki (GK) rats, a non-obese spontaneous model of NIDDM. We found a significant reduction (about 68%) in SERCA 3 isoform expression. Since SERCA 2 expression was not significantly reduced, these genes are independently regulated and probably play distinct roles in islets of Langerhans. The marked decrease of SERCA 3 expression may constitute a defect in Ca2+ signalling in GK rat islets which could be a component of NIDDM.

Animals↗

Characterization, cell-surface expression and ligand-binding properties of different truncated N-terminal extracellular domains of the ionotropic glutamate receptor subunit GluR1.

To identify the location of the first transmembrane segment of the GluR1 glutamate receptor subunit artificial stop codons have been introduced into the N-terminal domain at amino acid positions 442, 510, and 563, namely just before and spanning the proposed first two transmembrane regions. The resultant truncated N-terminal fragments of GluR1, termed NT1, NT2, and NT3 respectively were expressed in Cos-7 cells and their cellular distribution and cell-surface expression analysed using an N-terminal antibody to GluR1. All of the fragments were fully glycosylated and were found to be associated with cell membranes but none was secreted. Differential extraction of the cell membranes indicated that both NT1 and NT2 behave as peripheral membrane proteins. In contrast NT3, like the full subunit, has integral membrane protein properties. Furthermore only NT3 is expressed at the cell surface as determined by immunofluorescence and cell-surface biotinylation. Protease protection assays indicated that only NT3 had a cytoplasmic tail. Binding studies using the selective ligand [(3)H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate ([(3)H]AMPA) demonstrated that NT3 does not bind ligand. Together these results indicate that the first transmembrane domain of the GluR1 subunit lies between residues 509 and 562, that the N-terminal domain alone cannot form a functional ligand-binding site and that this domain can be targeted to the cell surface provided that it has a transmembrane-spanning region.

Animals↗

A unique combination of plasma membrane Ca2+-ATPase isoforms is expressed in islets of Langerhans and pancreatic beta-cell lines.

Changes in free intracellular Ca2+ concentration regulate insulin secretion from pancreatic beta-cells. The existence of steep Ca2+ gradients within the beta-cell requires the presence of specialized Ca2+ exclusion systems. In this study we have characterized the plasma membrane Ca2+-ATPases (PMCAs) which extrude Ca2+ from the cytoplasm. PMCA isoform- and subtype-specific mRNA expression was investigated in rodent pancreatic alpha- and beta-cell lines, and in human and rat islets of Langerhans using reverse-transcription PCR with primers flanking the calmodulin-binding region of rat PMCA. The expression pattern of PMCA 1 and 2 was conserved in different species and islet-cell types since both rat and human islets of Langerhans and all cell lines tested contained the 1b and 2b forms. PMCA 4 isoform subtypes, however, were expressed in a cell-type-specific manner since beta-cells expressed PMCA 4b only, whereas in islets of Langerhans, which contain alpha, beta, delta and polypeptide-secreting cells, PMCA 4a and 4b were simultaneously present. No evidence was obtained for the expression of PMCA 3. Characterization of the beta-cell Ca2+-pump protein showed that it shared several similarities with the erythrocyte PMCA. It is a P-type ATPase; its phosphorylated intermediate was stabilized by La3+; it reacted with a PMCA-specific antibody; and it was not N-glycosylate. However, the beta-cell PMCA had a higher molecular mass than that of the erythrocyte; this difference could be explained by either predominant translation of the PMCA2 form, which has a molecular mass 3-8 kDa higher than the erythrocyte PMCA 1 and 4 proteins, or by a possible sequence insertion. Thus a unique combination of functionally distinct PMCA isoforms (1b, 2b, 4b) participates in Ca2+ homoeostasis in the beta-cell.

Alternative Splicing↗

Therapy with pulsed electromagnetic fields in aseptic loosening of total hip protheses: a prospective study.

Aseptic loosening is the most common problem of hip arthroplasties, limiting its long term success. We report a study of pulsed electromagnetic field (PEMF) treatment in 24 patients with this complication. At the end of treatment, six months and one year later, pain and hip movements improved significantly with the exception of flexion and extension. There was significant improvement in both isotope scans and ultrasonography, but not in plain X-ray. The decreased pain and improved function suggest that PEMF is effective in improving symptoms of patients with loose hip replacement. No improvement, however, can be expected in patients with severe pain due to gross loosening.

Adult↗