Patients in end-stage renal disease undergoing renal replacement treatment (ESRD-RRT) are considered immunocompromised. The hemodialysis (HD) or peritoneal dialysis (PD) procedures seem to produce alterations of the immune status. Interest in immunosuppression has increased due to the poliomavirus BK (BKV) infection. Our study evaluated the prevalence of BKV infection in ESRD-RRT patients and viral replication on HD or PD. From 2006 to 2011 we selected 58 patients (34 males) in ESRD-RRT for inclusion in our study. BKV replication was evaluated by qualitative real-time polymerase chain reaction. In ESRD-RRT patients, the prevalence of BKV replication on plasma was 21%. We identified two groups of patients according to the dialysis procedure: 36 patients on HD (HD group) and 22 on PD (PD group). BKV replication in the HD group was 33% (12 of 36) versus 0% (0 of 22) in the PD group. Different age, number of months on RRT, and preserved diuresis was observed in the HD versus PD groups. With our results we can speculate that BKV infection in ESRD-RRT patients is linked to factors involved in the uremia-related immune dysfunction but also to specific mechanisms related to the different RRTs. PD is an option that could be associated with a better transplant outcome for patients undergoing kidney transplantation.
Infertility is a problem afflicting about 1/6 couples, and in 40% of cases this is primarily due to the male. Male infertility is a multifactorial pathology and it seems mainly related to sperm motility or sperm number. However, a diagnosis of infertility is frequently not followed by a precise explanation of its cause, reflecting our poor understanding of the spermatogenesis-related regulatory mechanisms and gene expression profiles. Therefore, this study was design to investigate the relative gene expression of a specific gene profile in ejaculate spermatozoa of men affected by infertility. This profile included 13 mitochondrial gene encoding subunits of respiratory chain and 7 nuclear sperm motility-related genes. We used values of progressive sperm motility (PR) to separate subjects affected by infertility into two groups, showing PR values higher (H group) or lower (L group) than the mean of the sample, and to classify fertile men (control group). We did not obtain a statistically significant difference in nuclear gene expression patterns in spermatozoa among these three groups. On the other hand, we observed an over-expression in 11/13 tested mitochondrial genes in the population of infertile males with altered sperm motility compared to the control group. This over-expression led us to speculate that there is an abnormal mRNA transcription of these 11 subunits, that impaired the normal energy supply ensuring sperm motility. Regarding the under-expression of 2/13 tested mitochondrial genes, we could assume that the spermatozoa mtDNA has accumulated mutations involving these two genes (CYB and ND4L). In conclusion, our results will provide useful information for the development of molecular diagnostic tools for clinical assessment of sperm health. However, further investigation into other sperm-related genes is needed to establish their roles in male fertility.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the neurotropic human polyomavirus JC (JCV) lytic infection of oligodendrocytes. PML was first described as a complication of lymphoproliferative disorders more than 50 years ago and emerged as a major complication of human immunodeficiency virus (HIV) infection in the 1980s. Despite the ubiquity of this virus, PML is rare and always seen in association with underlying immunosuppressive condition, such as HIV infection, autoimmune diseases, cancer, and organ transplantation. JCV remains quiescent in the kidneys, where it displays a stable archetypal non-coding control region (NCCR). Conversely, rearranged JCV NCCR, including tandem repeat patterns found in the brain of PML patients, have been associated with neurovirulence. The specific site and mechanism of JCV NCCR transformation is unknown. According to one model, during the course of immunosuppression, JCV departs from its latent state and after entering the brain, productively infects and destroys oligodendrocytes. Although the majority of PML cases occur in severely immunesuppressed individuals, PML has been increasingly diagnosed in patients treated with biological therapies such as monoclonal antibodies (mAbs) that modulate immune system functions: in fact, CD4+ and CD8+ T lymphopenia, resulting from this immunomodulatory therapy, are the primary risk factor. Furthermore, JCV reactivation in nonpermissive cells after treatment with mAbs, such as intestinal epithelial cells in Crohn's disease patients, in association with other host tumor-inducing factors, could provide valid information on the role of JCV in several malignancies, such as colorectal cancer.
End-stage liver disease (ESLD) and chronic kidney disease (CKD) patients are both immunocompromised populations but polyomavirus BK (BKV) replication before liver transplantation is rare. We evaluated BKV prevalence among liver transplant recipients with renal dysfunction and the possible role of CKD as a risk factor for BKV replication in ESLD. From 2010 to 2011 we selected 31 ESLD patients awaiting liver transplantation to identify, the presence of CKD: No CKD (n = 22; 18 males) and CKD group (n = 9; 5 males). BKV infection was defined on the basis of viremia evaluated using quantitative real-time polymerase chain reactions. The prevalence of viremia among the No CKD group was 14% versus 56% in the CKD group (Fisher test; P = .027).We hypothesized that the presence of CKD may represent an additional condition of immunologic dysfunction regarding antiviral surveillances other than the antibacterial one that characterizes ESLD immunodysfunction, which could have promoted BKV replication. The specific immunologic mechanisms involved in pretransplantation diseases may have a role in BKV reactivation that could become responsible for nephropathy after transplantation.
We describe a 79-year-old female with a chronic venous ulceration infected by Staphylococcus aureus and Enterococcus faecalis and not responsive to conventional treatments. The patient was treated with Methyl-Aminolaevulinate Photodynamic Therapy (MAL-PDT). After four weeks the cutaneous swabs become negative and we observed a significant clinical improvement. Therefore we suppose that MALPDT could represent a valid therapeutic option in the treatment of infected chronic ulcers.
This is a report concerning human polyomavirus JC (JCV) reactivation in a pediatric patient with Crohn's disease (CD) during the treatment with 5-aminosalicylic acid (5-ASA), a non-steroidal anti-inflammatory drug (NSAID). We examined 9 bioptic samples from three different bowel districts (ileum, cecum, rectum) of this child. These samples were analyzed by Quantitative PCR (Q-PCR) to investigate the presence of JCV DNA. JCV DNA was detected in one rectum biopsy taken two months after 5-ASA treatment. Although our result must be validated in a larger group of subjects and with a longer follow-up period, it underlines the importance of JCV monitoring in CD patients.
Herpes simplex virus (HSV) infection is one of the most common sexually transmitted viral diseases worldwide. HSV type 2 causes most genital herpes and HSV type 1 is usually transmitted via non-sexual contacts. We studied 109 pregnant women between January 2007 and December 2008, in relation to their age, condom use, number of sexual partners, age at first intercourse, parity and smoking habits. The aim of this study is to evaluate the prevalence of HSV cervical infection and HSV co-infection with other genital microorganisms associated with poor neonatal outcome. Our results show that of the 109 outpatients enrolled, 30% were HSV1 and/or HSV2 positive, of whom 30% were infected with both HSV1 and HSV2, 18% were infected with HSV1 alone and 52% with HSV2 alone. A significant association between HSV1 and HSV2 infection was found, and the prevalence of HSV2 infection in women infected with HSV1 was 63%. The prevalence of HSV1/2 varied in the presence of other vaginal microorganisms but a statistical significant association was not found. This pilot study is probably too small to obtain statistically significant results. Nevertheless, using these observed results, we calculated that about 530 patients with comparable features should be enrolled to detect an increase of 50% in HSV infection due to the presence of other genital infections and potential risk factors.
The basic molecular mechanisms regulating prostate cancer (PCA) development and progression are very poorly understood. Different tumor suppressor genes are implicated in PCA. In particular, since the mutation rate of the p53 gene is also low, researchers have speculated that an infectious agent might play an important role in PCA. Polyomaviruses are candidates for this agent. We selected a patient with a diagnosis of PCA and underwent radical prostatectomy, to investigate the presence of polyomavirus BK (BKV) sequences (urine and neoplastic tissues) and the mutation pattern of p53 gene. The results obtained showed the presence of BKV DNA and of p53 gene mutations in exons 6, 8 and 9. We speculate that BKV might contribute to cellular transformation process, triggered possibly by p53 gene mutations.