Aristolochic acid mutagenesis: molecular clues to the aetiology of Balkan endemic nephropathy-associated urothelial cancer

Balkan endemic nephropathy (BEN) is found in certain rural areas of the Balkans and affects at least 25,000 inhabitants. Of the many hypotheses on BEN, the Aristolochia hypothesis has recently gained ground substantiated by the investigations on aristolochic acid nephropathy (AAN). On both clinical and morphological grounds, AAN is very similar to BEN. That exposure to aristolochic acid (AA) of individuals living in endemic areas through consumption of bread made with flour contaminated with seeds of Aristolochia clematitis is responsible for BEN is an old hypothesis, but one which is fully consistent with the unique epidemiologic features of BEN. Here, we propose an approach to investigate AA-induced mutagenesis in BEN that can provide molecular clues to the aetiology of its associated urothelial cancer. The molecular mechanism of AA-induced carcinogenesis demonstrates a strong association between DNA adduct formation, mutation pattern and tumour development. A clear link between urothelial tumours, p53 mutations and AA exposure should emerge as more tumour DNA from BEN patients from different endemic areas becomes available for mutation analysis. We predict that the observed p53 mutation spectrum will be dominated by AT --> TA transversion mutations as has already been demonstrated in the human p53 gene of immortalized cells after exposure to AAI and urothelial tumours from BEN patients in Croatia. Moreover, the detection of AA-specific DNA adducts in renal tissue of a number of BEN patients and individuals living in areas endemic for BEN in Croatia provides new evidence that chronic exposure to AA is a risk factor for BEN and its associated cancer.     

Stability of dental implants after irradiation with an 830-nm low-level laser: a double-blind randomized clinical study

Little is known about the benefits of low-level laser therapy (LLLT) on improvement of stability of dental implants. The aim of this randomized clinical study was to assess the LLLT effect on implants stability by means of resonance frequency analysis (RFA). Thirty implants were distributed bilaterally in the posterior mandible of eight patients. At the experimental side, the implants were submitted to LLLT (830?nm, 86?mW, 92.1?J/cm², 0.25?J, 3?s/point, at 20 points), and on the control side, the irradiation was simulated (placebo). The first irradiation was performed in the immediate postoperative period, and it was repeated every 48?h in the first 14?days. The initial implant stability quotient (ISQ) of the implants was measured by means of RFA. New ISQ measurements were made after 10?days, 3, 6, 9, and 12?weeks. The initial ISQ values ranged from 65–84, with a mean of 76, undergoing a significant drop in stability from the 10th day to the 6th week in the irradiated group, and presenting a gradual increase from the 6th to the 12th week. The highest ISQ values were observed on the 10th day in the irradiated group, and the lowest in the 6th week in both groups. Under the conditions of this study, no evidence was found of any effect of LLLT on the stability of the implants when measured by RFA. Since high primary stability and good bone quality are of major relevancy for a rigid bone–implant interface, additional LLLT may have little impact macroscopically.     

Involvement of Renin-Angiotensin System in Pressure-Flow Relationship: Role of Angiotensin-converting Enzyme Gene Polymorphism

Background: The renin-angiotensin system is involved in blood pressure regulation. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is known to be associated with variation of plasma and cellular ACE concentrations. Furthermore, changes in arterial function have been suggested to be associated to the DD genotype. The aim of the study was to investigate the arterial vascular response to a physiologic stimulus (i.e., flow) according to the I/D ACE gene polymorphism.

Methods: Sixty patients scheduled for coronary artery bypass grafting (n = 24) or valve surgery (n = 36) under normothermic cardiopulmonary bypass were genotyped in a blind manner by polymerase chain reaction. Mean arterial pressure was measured at pump flows ranging from 1 to 3 l [middle dot] min-1 [middle dot] m-2 by 0.25 l [middle dot] min-1 [middle dot] m-2 step each 15 s, to obtain a pressure-flow relation. Independent factors associated with the variation of the slope of the pressure-flow relation curve were assessed by multivariate analysis.

Results: We found a D allelic frequency of 0.54. Patients were separated in two groups (DD, n = 16;ID/II, n = 44). There were no significant difference with regard to preoperative and intraoperative data between the two groups. DD patients had their pressure-flow relation curves shifted upward (with higher pressures as flow increased), indicating a lesser decrease in vascular resistance. Furthermore, DD genotype was the only independent predictor of the slope of the curves (21.5 +/- 4.2 vs. 18.1 +/- 5 mmHg/[l [middle dot] min-1 [middle dot] m-2] for DD and ID/II, respectively;P = 0.02; values are mean +/-SD).     

Family-based case-control study of MAOA and MAOB polymorphisms in Parkinson disease.

Monoamine oxidase (MAO) is an enzyme regulating metabolism of neurotransmitters such as dopamine. Two distinct forms of enzyme, encoded by genes MAOA and MAOB located on the X chromosome, have been considered as possible factors in the pathogenesis of Parkinson disease (PD). Previous association studies of PD and MAO genes reported inconsistent results. In this study, we used a large family-based data set to test associations between MAO genes and a risk of PD. The data set includes 298 female discordant sibpairs and 348 male discordant sibpairs. For this study, all subjects analyzed were white and families with known parkin mutations were removed. We analyzed 15 single nucleotide polymorphisms (SNPs) and a dinucleotide repeat marker in the MAO genes. Association was found with the intron 13 SNP of MAOB in the female subset (P = 0.02). No significant association was found in the male subset. Our results add to the evidence of involvement of MAOB in PD and suggest that the effect may be stronger in women.