Miklos Bodor

Characterization of the humanMDR1 gene

P-glycoprotein (Pgp), an ATP-dependent efflux transporter that protects the body from environmental toxins and xenobiotics, is encoded by the humanMDR1 gene. HumanMDR1 is located on chromosomal region 7q21. Although several different single nucleotide polymorphisms were shown to influence Pgp expression and activity, the reported length of theMDR1 gene in Genbank and other databases continues to evolve and varies between 6.3 kilobases (kb) and 210 kb. With DNA derived from human cell lines and tissues, we have characterized theMDR1 genomic sequence to be 209 kb.

Addition of chlorine during water purification reduces iodine content of drinking water and contributes to iodine deficiency

Drinking water is the major natural source of iodine in many European countries. In the present study, we examined possible sites of iodine loss during the usual water purification process. Water samples from 6 sites during the technological process were taken and analyzed for iodine content. Under laboratory circumstances, prepared iodine in water solution has been used as a model to test the effect of the presence of chlorine. Samples from the purification sites revealed that in the presence of chlorine there is a progressive loss of iodine from the water. In the chlorine concentrations employed in the purification process, 24-h chlorine exposure eliminated more than 50% of iodine when the initial iodine concentration was 250 µg/l or less. Iodine was completely eliminated if the starting concentration was 16 µg/l. We conclude that chlorine used during water purification may be a major contributor to iodine deficiency in European communities.

Rapid response to and long-term effectiveness of anti-CD20 antibody in conventional therapy resistant Graves’ orbitopathy: A five-year follow-up study

Abstract The aim of this investigations was to study the effectiveness of anti-CD20 antibody therapy in Graves’ orbitopathy (GO) resistant to glucocorticoids. Five patients were entered in the study. The protocol required no improvement of orbital status after a recent course of glucocorticoids. Activity of GO was confirmed by three independent techniques: clinical activity score (CAS), 99mTc-labeled diethylene triamine pentaacetic acid (99mTc DTPA) single photon emission computed tomography and magnetic resonance imaging. Rituximab (RTX) was given as weekly infusions of 375 mg/m2 body surface area for four weeks. The mean follow-up period was 67 (range 58–81) months. Improvement of GO has been observed in all patients: CAS before therapy was 6.5 ± 1.7 and decreased to 3.4 ± 1.6 by one month (p < 0.05) and remained unchanged (3.2 ± 1.7) at 12 months. No further CAS change, in either direction, was detected during the yearly follow-up visits. The mean DTPA uptake before therapy was 16.52 ± 4.51 MBq/cm3 and decreased to 11.97 ± 2.36 MBq/cm3 at one year (p < 0.002). The mean of T2 relaxation times before and one year after therapy were 96.91 ± 17.61 ms and 84.29 ± 9.41 ms, respectively (p < 0.001). The mean serum TSH receptor antibody (TRAb) levels before therapy, at the one month and one year control visits were 7.4 ± 3.4 U/L, 5.6 ± 4.5 U/L and 1.7 ± 1.5 U/L, respectively (p < 0.004). No correlation between changes of TRAb and activity parameters has been found. Anti-CD20 treatment seems to influence positively the clinical course of GO, and this effect seems to be stable for five years. To our knowledge, this is the longest published follow-up of RTX treatment in GO.

Human Liver Cytochrome P450 2D6 Genotype, Full-length Messenger Ribonucleic Acid, and Activity Assessed with a Novel Cytochrome P450 2D6 Substrate

The goal of this study was to develop and validate a cytochrome P450 (CYP) 2D6 probe substrate with improved sensitivity to elucidate the relationship of CYP2D6 ribonucleic acid transcript levels, genotype, and enzyme activity in human liver biopsy samples.

Thyroglobulin level at week 16 of pregnancy is superior to urinary iodine concentration in revealing preconceptual and first trimester iodine supply

Abstract Pregnant women are prone to iodine deficiency due to the increased need for iodine during gestation. Progress has recently occurred in establishing serum thyroglobulin (Tg) as an iodine status biomarker, but there is no accepted reference range for iodine sufficiency during pregnancy. An observational study was conducted in 164 pregnant women. At week 16 of gestation urinary iodine concentration (UIC), serum Tg, and thyroid functions were measured, and information on the type of iodine supplementation and smoking were recorded. The parameters of those who started iodine supplementation (≥150 μg/day) at least 4 weeks before pregnancy (n = 27), who started at the detection of pregnancy (n = 51), and who had no iodine supplementation (n = 74) were compared. Sufficient iodine supply was found in the studied population based on median UIC (162 μg/L). Iodine supplementation ≥150 μg/day resulted in higher median UIC regardless of its duration (nonusers: 130 μg/L vs. prepregnancy iodine starters: 240 μg/L, and pregnancy iodine starters: 205 μg/L, p < .001, and p = .023, respectively). Median Tg value of pregnancy starters was identical to that of nonusers (14.5 vs. 14.6 μg/L), whereas prepregnancy starters had lower median Tg (9.1 μg/L, p = .018). Serum Tg concentration at week 16 of pregnancy showed negative relationship (p = .010) with duration of iodine supplementation and positive relationship (p = .008) with smoking, a known interfering factor of iodine metabolism, by multiple regression analysis. Serum Tg at week 16 of pregnancy may be a promising biomarker of preconceptual and first trimester maternal iodine status, the critical early phase of foetal brain development.