Repair of oxidative DNA damage--an important factor reducing cancer risk. Minireview

Oxygen free radicals formed during normal aerobic cellular metabolism generate a variety of DNA lesions including modified bases, abasic sites and single strand breaks with blocked 3' termini. If left unrepaired, these damages may contribute to a number of degenerative processes, including cancer and aging. In most organisms, the repair of oxidative DNA lesions is supposed to be handled by the base excision repair (BER) pathway. BER is a multistep process that involves the sequential activity of several proteins, many of them were isolated and functionally characterized using the simple prokaryotic and lower eukaryotic model systems, Escherichia coli and Saccharomyces cerevisiae, respectively. As the amino acid sequence of DNA repair proteins is often well conserved from bacteria to man, our understanding of BER in higher eukaryotes drives extensively from the microbial models, namely from the yeast S. cerevisiae. Thus, results obtained on a simple yeast model are a source of new information, which can be used as a paradigm for all eukaryotic cells.     

Further characterization of the role of Pso2 in the repair of DNA interstrand cross-link-associated double-strand breaks in Saccharomyces cerevisiae

DNA interstrand cross-links (ICL) are thought to be one of the most lethal forms of DNA damage. Therefore, they present a colossal challenge for the DNA damage response and repair pathways. In Saccharomyces cerevisiae, ICL repair utilizes factors from all of the three major repair groups: nucleotide excision repair (RAD3 epistasis group), post-replication repair (RAD6 epistasis group) and recombinational repair (RAD52 epistasis group). Moreover, there are additional factors significantly influencing the repair of ICL in this organism. These have been designated PSO1-10 based on the psoralen sensitive phenotype of the corresponding mutants. Phenotype of the pso2 mutant suggests that Pso2 is not involved in incision step of ICL repair, but it rather functions in some downstream event such as processing of DNA ends created during generation of ICL-associated double-strand breaks (DSB). In order to address the question whether function of Pso2 in the repair of ICL-associated DSB could be mediated through protein-protein interactions, we have conducted a comprehensive two-hybrid screen examining a possibility of interaction of Pso2 with Yku70, Yku80, Nej1, Lif1, Dnl4, Rad50, Mre11, Xrs2, Rad51, Rad52, Rad54, Rad55, Rad57, Rad59 and Rdh54. Here we show that Pso2 associates with none of the above DSB repair proteins, suggesting that this protein very likely does not act in the repair of ICL-associated DSB via crosstalk with DSB repair machinery. Instead, its function in this process seems to be rather individual.     

Adrenal incidentalomas and the metabolic syndrome--are there any differences between adenoma and hyperplasia?

Authors evaluated the prevalence of symptoms of the metabolic syndrome and insulin resistance in 25 patients with adrenal incidentalomas (10 men, 15 women) of the mean age 57.9+/-15 years. 15 patients had adrenal adenoma determined by CT or MR scan and 10 had unilateral or bilateral hyperplasia. The prevalence of obesity was 72%, arterial hypertension 60%, diabetes mellitus or impaired glucose tolerance 28%, hyperlipidemia 56% and hyperuricemia 20%, respectively, which is more frequent occurrence than that in normal human population. Patients with adrenal adenomas had mildly but significantly higher body mass index (BMI, p<0.05) and insulin resistance calculated as HOMA IR (p<0.05) and FIRI (p<0.05) and significantly higher values of serum ferritin (p<0.01). Plasma cortisol values were slightly but not significantly higher in the group with adrenal adenomas. Authors conclude that adrenal adenomas are probably more related to the metabolic syndrome than adrenal hyperplasia.     

Morphology and distribution of neurons expressing serotonin 5-HT1A receptors in the rat hypothalamus and the surrounding diencephalic and telencephalic areas

Disorders of serotonergic neurotransmission are involved in disturbances of numerous hypothalamic functions including circadian rhythm, mood, neuroendocrine functions, sleep and feeding. Among the serotonin receptors currently recognized, 5-HT_1A receptors have received considerable attention due to their importance in the etiology of mood disorders. While previous studies have shown the presence of 5-HT_1A receptors in several regions of the rat brain, there is no detailed map of the cellular distribution of 5-HT_1A receptors in the rat diencephalon.In order to characterize the distribution and morphology of the neurons containing 5-HT_1A receptors in the diencephalon and the adjacent telencephalic areas, single label immunohistochemistry was utilized. Large, multipolar, 5-HT_1A-immunoreactive (IR) neurons were mainly detected in the magnocellular preoptic nucleus and in the nucleus of diagonal band of Broca, while the supraoptic nucleus contained mainly fusiform neurons. Medium-sized 5-HT_1A-IR neurons with triangular or round-shaped somata were widely distributed in the diencephalon, populating the zona incerta, lateral hypothalamic area, anterior hypothalamic nucleus, substantia innominata, dorsomedial and premamillary nuclei, paraventricular nucleus and bed nucleus of stria terminalis.The present study provides schematic mapping of 5-HT_1A-IR neurons in the rat diencephalon. In addition, the morphology of the detected 5-HT_1A-IR neural elements is also described. Since rat is a widely used laboratory animal in pharmacological models of altered serotoninergic neurotransmission, detailed mapping of 5-HT_1A-IR structures is pivotal for the neurochemical characterization of the neurons containing 5-HT_1A receptors.     

Preconceptional screening of sexually transmitted infections/diseases

Hungarian Preconceptional Care includes the preconceptional screening of sexually transmitted infections/disorders (STD) and vaginal candidosis of potential mothers and pyospermia of potential fathers. The aim of this study was to evaluate the effect of this screening and treatment for the rate of preterm births. Clinical and subclinical vaginal candidiasis (asymptomatic candida colonisation), combination of STD and vaginal candidiasis, STD without vaginal candidiasis, finally women without STD and vaginal candidiasis as references were evaluated in 4,672 pregnant women. The association of STD in pregnant women with higher risk of preterm birth was confirmed. However, an association was also found between clinically diagnosed vaginal candidiasis, asymptomatic candida colonisation, and a higher risk for preterm births. This risk was reduced with clotrimazole treatment. However, pregnant women without recognized STD and/or vaginal candidiasis had a higher risk for preterm birth than pregnant women with STD or vaginal candidiasis after appropriate treatment. Thus the conclusion of the study is that the preconceptional screening of STD and vaginal candidiasis followed by appropriate treatment is important to prevent a certain part of preterm birth but it is necessary to improve the efficacy of the previously used methods for this screening.     

Clinical evaluation of autopsy in the aged

On a general medical department with 54 beds, 801 patients (8.6%) expired between 1980 and 1984 in 780 of them (97.3%) autopsy has revealed. 58.4% of expired patients were over seventy years. In this age group autopsy data diverged from the underlying disease in 9.58%, however this ratio of patients under seventy was 8.56%, as well. Mistake of clinical diagnosis in the direct cause of death was 18.9% in the group of under seventy and 21.3% of over seventy. The highest ratio of mistakes in the underlying disease has occurred in diseases of malignancies (progressing with age). Referring to the direct cause of death, undiagnosed pulmonary embolism had in each age group an equal high ratio. Because of the augmented multimorbidity with age the autopsy in the elderly can serve for an improvement of diagnosis.     

The effect of preconceptional multivitamin supplementation on the menstrual cycle

The database of the Hungarian randomised controlled trial of periconceptional multivitamin supplementation for the prevention of neural-tube defects was used to evaluate the length of the pre- and postovulatory phases of the menstrual cycle before and during multivitamin supplementation. The female cycle was more regular (i.e., the variance was lower) during the multivitamin supplementation.