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High-Density Real-Time PCR-Based in Vivo Toxicogenomic Screen to Predict Organ-Specific Toxicity

Toxicogenomics, based on the temporal effects of drugs on gene expression, is able to predict toxic effects earlier than traditional technologies by analyzing changes in genomic biomarkers that could precede subsequent protein translation and initiation of histological organ damage. In the present study our objective was to extend in vivo toxicogenomic screening from analyzing one or a few tissues to multiple organs, including heart, kidney, brain, liver and spleen. Nanocapillary quantitative real-time PCR (QRT-PCR) was used in the study, due to its higher throughput, sensitivity and reproducibility, and larger dynamic range compared to DNA microarray technologies. Based on previous data, 56 gene markers were selected coding for proteins with different functions, such as proteins for acute phase response, inflammation, oxidative stress, metabolic processes, heat-shock response, cell cycle/apoptosis regulation and enzymes which are involved in detoxification. Some of the marker genes are specific to certain organs, and some of them are general indicators of toxicity in multiple organs. Utility of the nanocapillary QRT-PCR platform was demonstrated by screening different references, as well as discovery of drug-like compounds for their gene expression profiles in different organs of treated mice in an acute experiment. For each compound, 896 QRT-PCR were done: four organs were used from each of the treated four animals to monitor the relative expression of 56 genes. Based on expression data of the discovery gene set of toxicology biomarkers the cardio- and nephrotoxicity of doxorubicin and sulfasalazin, the hepato- and nephrotoxicity of rotenone, dihydrocoumarin and aniline, and the liver toxicity of 2,4-diaminotoluene could be confirmed. The acute heart and kidney toxicity of the active metabolite SN-38 from its less toxic prodrug, irinotecan could be differentiated, and two novel gene markers for hormone replacement therapy were identified, namely fabp4 and pparg, which were down-regulated by estradiol treatment.

Anticancer and Multidrug Resistance-Reversal Effects of Solanidine Analogs Synthetized from Pregnadienolone Acetate

A set of solanidine analogs with antiproliferative properties were recently synthetized from pregnadienolone acetate, which occurs in Nature. The aim of the present study was an in vitro characterization of their antiproliferative action and an investigation of their multidrug resistance-reversal activity on cancer cells. Six of the compounds elicited the accumulation of a hypodiploid population of HeLa cells, indicating their apoptosis-inducing character, and another one caused cell cycle arrest at the G2/M phase. The most effective agents inhibited the activity of topoisomerase I, as evidenced by plasmid supercoil relaxation assays. One of the most potent analogs down-regulated the expression of cell-cycle related genes at the mRNA level, including tumor necrosis factor alpha and S-phase kinase-associated protein 2, and induced growth arrest and DNA damage protein 45 alpha. Some of the investigated compounds inhibited the ABCB1 transporter and caused rhodamine-123 accumulation in murine lymphoma cells transfected by human MDR1 gene, expressing the efflux pump (L5178). One of the most active agents in this aspect potentiated the antiproliferative action of doxorubicin without substantial intrinsic cytostatic capacity. The current results indicate that the modified solanidine skeleton is a suitable substrate for the rational design and synthesis of further innovative drug candidates with anticancer activities.

Placental three-dimensional power Doppler indices in mid-pregnancy and late pregnancy complicated by gestational diabetes mellitus

The aim of our study was to evaluate placental three‐dimensional power Doppler indices in diabetic pregnancies in the second and third trimesters and to compare them with those of the normal controls.

Spherical LDH-Ag°-montmorillonite heterocoagulated system with a pH-dependent sol-gel structure for controlled accessibility of AgNPs immobilized on the clay lamellae.

Aqueous suspensions of spherical ZnMgAl-layered double hydroxides [LDH(sph)] and antibacterial silver nanoparticles (AgNPs) deposited on the lamellae of montmorillonite were used for the synthesis of composites, which behave like coherent gels at low pH (≲4.5) and incoherent sols at higher pH (≳4.5). The composition of the composite was chosen as LDH(sph)/Ag°-montm. = 25:75 wt % in order to ensure a sol-gel transition that can also be characterized by viscometry. This pH-sensitive heterocoagulated system consisting of oppositely charged colloid particles was suitable for the release of antimicrobial AgNPs immobilized on the clay lamellae via a pH-controlled gel-sol transition. The heterocoagulation process was also characterized by surface charge titration measurements. Spherical LDH/Ag°-montmorillonite composite samples were identified by X-ray diffraction (XRD) measurements. The morphological properties of the composites were studied, and the presence of the heterocoagulated structure was confirmed by scanning electron microscopy (SEM). The nanoscale structure of the LDH(sph)-Ag°-montmorillonite composite obtained was also verified by small-angle X-ray scattering (SAXS), and the rheological characteristics were studied at various pH values. The viscosity and yield value of the composite decreased by an order of magnitude upon increasing the pH from 3.0 to 5.5. The sol-gel transition of the composite suspension was reversible in the previously mentioned pH range.

Monitoring of fetal heart rate via iPhone

Recording of fetal heart rate can be reassuring for the mother about the fetus’ wellbeing. Our smart phone application can detect, record and evaluate fetal heart rate at any time. This method is based on sound wave thus free from the effects of ultrasound, and can be used all day without harming the fetus. It does not require medical assistance and easy to use at home. It reduces the queue at outpatient care units, helps pregnant women to relieve stress by listening to their unborn baby’s heartbeat. It improves mother-child relationship yet sends an alarming message if further examinations are needed to prevent the consequences of hypoxia.

Unusual Clinical History of a Male Infant with Edwards Syndrome

Edwards syndrome (trisomy of chromosome 18) is generally characterized by the disorders of central nervous system, as well as the musculoskeletal and genitourinary systems. In majority of the cases with trisomy 18 the following malformations can be found: ventricular septal defect, horseshoe kidneys, oesophageal atresia, omphalocele, facial clefts, diaphragmatic hernias and genital hypoplasia. We report a male patient with Edwards syndrome. The boy had a partial agenesis of corpus callosum, oesophageal atresia with tracheo-oesophageal fistula, renal agenesis, ventricular septal defect, Dandy-Walker cyst and low-set malformed ears. The first three features are unique based on previous literature reports on trisomy 18. This report allows a further delineation of the trisomy 18 syndrome.

Use of Infertility Handling Among Women of Reproductive Age

Our primary objective was to develop a mobile application for monitoring the changes of menstrual cycle for clinical treatment planning. Participating woman can use the application called “Infertility Handling”, which will be soon available from Google Play Store for general public. This Android-based application provides basic biological and physiological information to women using the application at different stages of the cycle. They will receive useful help and advice concerning their health. The application provides also quick and convenient information gathering for short and long-term management of patient’s treatment and excellent tool for the personal medical monitoring. In this paper we present a short summary of the developed application.

Knowledge and attitudes of female university students on menstrual cycle and contraception

Abstract Socioeconomic changes, as well as the development of new contraceptive modalities may influence women’s preferences in the selection of a method of contraception. The aim of this study was to evaluate the knowledge, opinions and attitudes of female university students regarding the menstrual cycle, sexual health and contraception. A questionnaire-based survey was conducted among 2572 female university students in Hungary, Romania and Serbia, between November 2009 and January 2011. A higher proportion of students of health sciences than students of other faculties had appropriate knowledge of the fertile period within a menstrual cycle: 86.0%, 71.5% (p = .02) and 61.1% vs. 71.9% (p < .001), 59.8% and 43.2% (p < .001) in Hungary, Romania and Serbia, respectively. Overall, more than 69% of the female university students believed in the need for monthly menstruation in order to be healthy; however, merely 30 to 40% of them wished to have monthly bleeding. In general, the respondents were aware of the importance of menstruation in relation to sexual health; however, they wished to suppress the menstruation-related symptoms. Differences in the knowledge and attitudes of female university students of the three assessed countries may be explained in part by cultural differences, and in part by the nature of their studies.

P05.30: What is fetal kidney length in toxemia with renal hyperechogenicity?

5 mmHg (P = 0.03); mean arterial pressure 97 ± 7 vs. 92 ± 4 mmHg (P = 0.03); Total Vascular Resistance 1642 ± 223 vs. 1221 ± 168 dyne·s·cm-5 (P =< 0.000); Cardiac Output 4.8 ± 0.7 vs. 6.1 ± 0.8 (P = 0.002); presence of EDF 0/12 (0.0%) vs. 10/12 (83.3%) (P = 0.02); Umbilical PI 2.1 ± 0.13 vs. 1.63 ± 0.24 (p < 0.000); abdominal circumference centile 3 ± 1 vs 7 ± 2 (P = 0.005). Conclusions: The progression of fetal growth restriction might be restrained acting on maternal cardiac function.