Results, questions, perspectives of a study on human polyomavirus BK and molecular actors in prostate cancer development

Background: Prostate cancer (PC) is a common tumor in Western countries. Several risk factors play significant roles. MYC, BIRC5/survivin, CDC25 and P53 may contribute to PC risk. As demonstrated, human Polyomavirus BK (BKV) could affect cellular homeostasis contributing to PC pathogenesis. Materials and Methods: Biological samples were collected from PC patients. Viral RNA was searched using quantitative polymerase chain reaction (PCR), whereas a qualitative PCR was employed to find particular viral sequences. Proper size amplicons were analyzed. Single nucleotide polymorphisms (SNPs) were detected in p53 coding regions by means of a specific PCR. C-MYC, BIRC5/survivin and CDC25 gene expression was investigated using a Retro Transcriptional Quantitative PCR. Results: Viral DNA copy number was higher in cancer tissues taken from Gleason score 9 patients with Gleason score 7. Different p53 mutated compared to patients exons were found according to tumor advanced stage and a statistical significant correlation was found between Gleason score and p53 mutational rate. C-MYC, BIRC5/survivin and CDC25 expression was de-regulated according to the literature. Conclusion: The presence of BKV and its variants in transformed cells does not exclude viral pressure in cell immortalization. Expression of other target genes evidenced a significant change in their regulation, useful for cancer drug discovery and therapies

High frequency of JCV DNA detection in prostate cancer tissues

BACKGROUND: Prostate cancer (PC) represents the most frequently diagnosed cancer in men. Exposure to infectious agents has been considered to induce prostatic inflammation and cancerous transformation. Controversial data exist concerning the role of the human polyomaviruses BK (BKV) and JC (JCV) in PC etiology. Therefore, a possible association between these polyomaviruses and PC was investigated. MATERIALS AND METHODS: Urine, blood and fresh prostatic tissue specimens were collected from 26 patients with PC. The presence of BKV and JCV, the possible non-coding control region (NCCR) variations and the genotyping analysis of viral protein 1 (VP1) of both viruses were assessed. RESULTS: Data showed a preferential viral re-activation in the urinary compartment and a statistically significant prevalence of JC viruria and of BKV in PC tissues. A BKV DDP-like NCCR sequence was isolated in two patients, whereas JCV NCCR was consistently of an archetypal structural organization. A prevalence of the European genotypes was observed for both viruses. CONCLUSION: Our data demonstrated the presence of JCV DNA in 14/24 (58.3%) cancerous prostatic tissue specimens, confirming the results obtained in a previous study, in which JCV has been defined as common inhabitant of the prostate, and opening the discussion about its potential role in PC

Physical Activity and Renal Transplantation

Renal transplantation is burdened by high cardiovascular risk because of increased prevalence of traditional and disease-specific cardiovascular risk factors and, consequently, patients are affected by greater morbidity and mortality. In renal transplanted patients, healthy lifestyle and physical activity are recommended to improve overall morbidity and cardiovascular outcomes. According to METs (Metabolic Equivalent Task; i.e. the amount of energy consumed while sitting at rest), physical activities are classified as sedentary (<3.0 METs), of moderate-(3.0 to 5.9 METs) or vigorous-intensity (≥6.0 METs). Guidelines suggest for patients with chronic kidney disease an amount of physical activity of at least 30 minutes of moderate-intensity activity five times per week (min 450 MET-minutes/week). Data on physical activity in renal transplanted patients, however, are limited and have been mainly obtained by mean of non-objective methods. Available data suggest that physical activity is low either at the start or during renal transplantation and this may be associated with poor patient and graft outcomes. Therefore, in renal transplanted patients more data on physical activity obtained with objective, accelerometer-based methods are needed. In the meanwhile, physical activity have to be considered as an essential part of the medical care for renal transplanted recipients

&quot;Dietaly&quot;: Practical issues for the nutritional management of CKD patients in Italy

Evidence exists that nutritional therapy induces favorable metabolic changes, prevents signs and symptoms of renal insufficiency, and is able to delay the need of dialysis. Currently, the main concern of the renal diets has turned from the efficacy to the feasibility in the daily clinical practice. Herewith we describe some different dietary approaches, developed in Italy in the last decades and applied in the actual clinical practice for the nutritional management of CKD patients. A step-wise approach or simplified dietary regimens are usually prescribed while taking into account not only the residual renal function and progression rate but also socio-economic, psychological and functional aspects. The application of the principles of the Mediterranean diet that covers the recommended daily allowances for nutrients and protein (0.8 g/Kg/day) exert a favorable effect at least in the early stages of CKD. Low protein (0.6 g/kg/day) regimens that include vegan diet and very low-protein (0.3-0.4 g/Kg/day) diet supplemented with essential amino acids and ketoacids, represent more opportunities that should be tailored on the single patient’s needs. Rather than a structured dietary plan, a list of basic recommendations to improve compliance with a low-sodium diet in CKD may allow patients to reach the desired salt target in the daily eating. Another approach consists of low protein diets as part of an integrated menu, in which patients can choose the “diet” that best suits their preferences and clinical needs. Lastly, in order to allow efficacy and safety, the importance of monitoring and follow up of a proper nutritional treatment in CKD patients is emphasized

The mitochondrial DNA control region shows genetically correlated levels of heteroplasmy in leukocytes of centenarians and their offspring

<p>Abstract</p> <p>Background</p> <p>Studies on heteroplasmy occurring in the mitochondrial DNA (mtDNA) control region (CR) in leukocytes of centenarians and younger subjects have shown that the C150T somatic transition is over-represented in centenarians. However, whether the occurrence/accumulation of heteroplasmy is a <it>phenotypic consequence </it>of extreme ageing or a <it>genetically controlled event </it>that may favor longevity is a question that deserves further attention. To clarify this point, we set up a Denaturing High Performance Liquid Chromatography (DHPLC) protocol to quantify mtDNA CR heteroplasmy. We then analyzed heteroplasmy in leukocytes of centenarians (100 subjects), their offspring and nieces/nephews (200 subjects, age-range 65–80 years, median age 70 years), and in leukocytes of 114 control subjects sex- and age-matched with the relatives of centenarians.</p> <p>Results</p> <p>The centenarians and their descendants, despite the different ages, showed similar levels of heteroplasmy which were significantly higher than levels in controls. In addition we found that heteroplasmy levels were significantly correlated in parent-offspring pairs (r = 0.263; p = 0.009), but were independent of mtDNA inherited variability (haplogroup and sequence analyses).</p> <p>Conclusion</p> <p>Our findings suggest that the high degree of heteroplasmy observed in centenarians is genetically controlled, and that such genetic control is independent of mtDNA variability and likely due to the nuclear genome.</p

Importance of Echocardiography and Clinical "Red Flags" in Guiding Genetic Screening for Fabry Disease

Aim of this study was to evaluate, in a metropolitan area not already explored, the prevalence of Anderson-Fabry disease, by genetic screening, in patients with echocardiographic evidence of left ventricular hypertrophy (LVH) of unknown origin and "clinical red flags"

Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects