Biomedical subjects

Csaba Papp

Publications and source records attributed to Csaba Papp.

5 recordsLinked to original sources

PubMed2024

The Neosartorya (Aspergillus) fischeri antifungal protein NFAP2 has low potential to trigger resistance development in Candida albicans in vitro.

Due to the increase in the number of drug-resistant Candida albicans strains, new antifungal compounds with limited potential for the development of resistance are urgently needed. NFAP2, an antifungal protein (AFP) secreted by Neosartorya (Aspergillus) fischeri, is a promising candidate. We investigated the ability of C. albicans to develop resistance to NFAP2 in a microevolution experiment compared with generic fluconazole (FLC). C. albicans adapted to only 1× minimum inhibitory concentration (MIC) of NFAP2, which can be considered tolerance rather than resistance, compared with 32× MIC of FLC. Genome analysis revealed non-silent mutations in only two genes in NFAP2-tolerant strains and in several genes in FLC-resistant strains. Tolerance development to NFAP2 did not influence cell morphology. The susceptibility of NFAP2-tolerant strains did not change to FLC, amphotericin B, micafungin, and terbinafine. These strains did not show altered susceptibility to AFPs from Penicillium chrysogenum, except one which had less susceptibility to Penicillium chrysogenum antifungal protein B. FLC-resistant strains had decreased susceptibility to terbinafine and NFAP2, but not to other drugs and AFPs from P. chrysogenum. NFAP2-tolerant and FLC-resistant strains showed decreased and increased NFAP2 binding and uptake, respectively. The development of tolerance to NFAP2 decreased tolerance to cell wall, heat, and UV stresses. The development of FLC resistance increased tolerance to cell wall stress and decreased tolerance to heat and UV stresses. Tolerance to NFAP2 did not have significant metabolic fitness cost and could not increase virulence, compared with resistance to FLC.IMPORTANCEDue to the increasing number of (multi)drug-resistant strains, only a few effective antifungal drugs are available to treat infections caused by opportunistic Candida species. Therefore, the incidence of hard-to-treat candidiasis has increased dramatically in the past decade, and the demand to identify antifungal compounds with minimal potential to trigger resistance is substantial. The features of NFAP2 make it a promising candidate for the topical treatment of Candida infection. Data on the development of resistance to antifungal proteins in Candida albicans are lacking. In this study, we provide evidence that NFAP2 has a low potential to trigger resistance in C. albicans in vitro, and the developed tolerance to NFAP2 is not associated with severe phenotypic changes compared with development of resistance to generic fluconazole. These results suggest the slow emergence of NFAP2-resistant Candida strains, and NFAP2 can reliably be used long-term in the clinic.

Antifungal Agents↗

PubMed2003

Chorionic villus sampling and amniocentesis: what are the risks in current practice?

PURPOSE OF REVIEW: Public demand for genetic counselling and prenatal diagnosis has increased during the past decade. As invasive diagnostic methods, such as chorionic villus sampling and amniocentesis, still have an important role to play in evaluating the fetus, one of the most important questions to address during genetic counselling is the procedure-related risk of these techniques. RECENT FINDINGS: The possible factors modifying the specific risk of the actual fetus are discussed, together with factors that have an impact on procedure-related fetal loss and other complications. Risk factors regarding twin pregnancies, first and second-trimester chorionic villus sampling, early and mid-trimester amniocentesis are discussed separately. New developments have recently occurred in the laboratory techniques used in prenatal diagnosis. Their impact on genetic counselling and the employment of invasive techniques are also addressed. SUMMARY: During genetic counselling, an individually tailored risk assessment needs to be established before any invasive procedure. This should take into account all the factors modifying the specific risk for aneuploidy or other disorders of the fetus, as well as the actual procedure-related risks.

Amniocentesis↗

PubMed2002

Rapid diagnosis of triploidy of maternal origin using fluorescent PCR and DNA fragment analysis in the third trimester of pregnancy.

OBJECTIVES: Triploidy is a common cause of spontaneous abortion in the very early stages of pregnancy. It is very rare for a prenatal diagnostic center to discover triploidy in the third trimester of pregnancy. A pregnant woman in the third trimester was referred to our genetic counselling clinic because of abnormal ultrasound findings. We planned to test for the most common chromosomal abnormalities. METHODS: We performed ultrasound examination, chorionic villus sampling, karyotyping and fluorescent-polymerase chain reaction (F-PCR) and fragment analysis. RESULTS: We diagnosed a 69,XXX karyotype fetus in the 31st week of gestation, based on a short tandem repeat (STR) pattern typical for triploidy, which was confirmed by karyotyping. The comparison of the fetal and parental STR patterns showed maternal origin of the extra haploid chromosome set. CONCLUSIONS: STR analysis of fluorescent-PCR and DNA fragment analysis is a rapid and reliable alternative to karyotyping for detection of certain aneuploidies. The method is also suitable for the determination of the origin of the extra chromosome set.

Abortion, Eugenic↗

PubMedDate not supplied

Chorionic villus sampling: a 15-year experience.

The authors describe experiences gained over the period of 1984-1999 at two medical centers with chorionic villus sampling (CVS). Altogether 1,149 CVSs had been performed between the 10th and 32nd gestational weeks. Prior to 1993 the transcervical approach (TC-CVS), after 1994 the transabdominal method (TA-CVS) was used. Analysis of data collected within the framework of this study was based on the following factors: indications for sampling, complications and incidence of pregnancy loss. 91.6% of the CVSs were carried out for the purposes of cytogenetic examination of the fetus. Over the past few years an increasing number of procedures had been carried out for molecular-genetic tests (7.6% of the total number of cases). Though the primary indication for cytogenetic tests was the advanced age of the mother, a remarkable increase in the number of samplings had taken place for the purpose of examining "suspicious ultrasound findings", minor anomalies detected by ultrasound. In this group the proportion of pathological cases was significantly higher (14%) than in all the other samplings, carried out for other indications. This data in itself underlines the importance of ultrasound screening performed in the 18-20th weeks of gestation. Over the first half of the period being reviewed (1984-1993, TC-CVS), a fetal loss of 4.8% occurring within 3 weeks from the date of sampling, dropped to 1.7% in the period subsequent to year 1994 (TA-CVS). In cases of TA-CSV, both the complications and spontaneous abortions were fewer. In 74.1% of the cases studied, birth had taken place after the 37th week of gestation. Premature births (6.4%) and stillbirth rate (1.1%) did not exceed normal rates observed in the general population. On the basis of our results, it is safe to say that in prenatal diagnosis, TA-CVS is a real alternative method of mid-trimester amniocentesis and it is recommended for use at any stage of the pregnancy.

Adolescent↗

PubMedDate not supplied

Pre- and perinatal relations of hemophilia A and B.

OBJECTIVE: The authors conducted a retrospective study of obstetric and genetic data, obstetric problems, and pregnancy outcome by investigating 149 pregnancies of patients who received genetic counselling because of hemophilia A or B over a 20-year period. METHODS: In cases with a heterozygous mother, fetal sex was determined. In 23 of 35 cases with male fetuses, a DNA examination was performed. In cases with hemophilic male fetuses, the couple made a decision on whether or not to continue the pregnancy after thorough counselling regarding genetic risk. Hemophilia A occurred 135 pregnancies (98 pregnancies from 55 heterozygous mothers and 37 pregnancies from 20 hemophilic fathers). Hemophilia B occurred in 14 pregnancies (9 pregnancies from 3 heterozygous mothers and 5 pregnancies from 4 hemophilic fathers). RESULTS: In pregnant women who were carriers of hemophilia A, 32 of the fetuses were male, and DNA examinations were performed in 22 cases. In 16 cases abortions were induced (in 10 cases hemophilia was confirmed by DNA examination), and in 4 of 16 deliveries affected males were born (the disease was confirmed by DNA examination during pregnancy). Of 3 confirmed male fetuses of heterozygous women with hemophilia B, 1 healthy male was born. In 2 cases abortions were induced (in 1 case on the basis of DNA diagnosis). CONCLUSIONS: In cases of heterozygous mothers (hemophilia A and B together) the rate of spontaneous abortions was 13.1%. The rates of premature deliveries (8.2%) and cesarean sections (8.2%) were no higher than national average. The rate of bleeding complications during pregnancy was 18.7%, in 2.7% of cases transfusions were necessary. In case of hemophilic fathers (in heterozygous female fetuses the hemostasis may change from the fetal side) the rate of bleeding complications during pregnancy was 18.2%. In terms of deliveries, obstetrical bleeding complications occurred in 12.2%, atonia in 2%, curettage after delivery in 4.1%, and transfusion in 10.2% of the heterozygous mothers with hemophilia A and B combined. Neonatal complications were cerebral hemorrhage in 1 case and bleeding from the umbilical stump in another case (both newborns were hemophilic males). In connection with delivery, there was no sign of hematoma development on the skull of the newborns, nor were transfusions necessary. In cases of paternal disease the rate of curettage was 6.7% and there were no neonatal or other obstetrical complications.

Delivery, Obstetric↗