Simultaneous BK Polyomavirus (BKPyV)-associated nephropathy and hemorrhagic cystitis after living donor kidney transplantation

BK polyomavirus (BKPyV) commonly reactivates after kidney transplantation, and can cause polyomavirus-associated nephropathy (PyVAN), whereas after allogeneic stem cell transplantation the most frequent manifestation of BKPyV is polyomavirus-associated hemorrhagic cystitis (PyVHC). Despite high-level BKPyV replication in both, the pathogenesis and manifestation of both BKPyV entities appears to differ substantially. We describe an unusual case of simultaneous PyVAN and PyVHC presenting with acute symptoms in a BKPyV-IgG positive recipient eight months after kidney transplantation from a haploidentical living donor, who was BKPyV-IgG negative. Symptoms of cystitis and viremia subsided rapidly after reduction of immunosuppression. (C) 2015 Elsevier B.V. All rights reserved.Peer reviewe

High-level JCPyV viruria after kidney transplantation-Clinical and histopathological findings

Background:The significance of JC polyomavirus (JCPyV) after kidney transplantation ranges from irrelevant to full-blown nephropathy or PML. Objectives: To investigate the clinical significance of high-level JCPyV viruria and JCPyV primary infections after kidney transplantation. Study design: JCPyV viruria was detected in routine screening by quantitative real-time PCR in 40/238 kidney transplant recipients and was high-level (> 10(7)copies/ml) in 17 patients. A protocol biopsy at the time of JCPyV viruria was available from 10 patients. Results: Peak urine viral loads were 1.0 x 10(7)-2.5 x 10(9)copies/ml in the 17 high-level viruria patients. 6/15 (40%) patients with high-level JCPyV viruria with pretransplant sera available were JCPyV IgG negative suggesting that JCPyV viruria resulted from the donor graft in most cases. No acute graft dysfunction was associated with JCPyV viruria. No positive SV40 staining was detected in protocol biopsies, and nospecific histopathology was associated with high-level viruria; JCPyV nephropathy was not found. No differences were seen in histopathology or graft function at 3 years in patients with high-level viruria compared to non-JCPyV viruric patients transplanted during the same time period, and outcome was similar in patients with presumably primary and reactivated JCPyV. The mean estimated GFR at last follow-up was 44 ml/min (range 12-60 ml/min). One graft with high-level viruria was lost 9 years posttransplant due to recurrent IgA nephropathy Conclusions: High-level JCPyV viruria seems to be associated with primary JCPyV infection reflecting the average seroprevalence of 60%, but is not stringently associated with inferior graft function or survival, or histopathological changes. c 2016 Elsevier B.V. All rights reserved.Peer reviewe

Passing otoacustic emissions as a complementar method in the topodiagnosis of the neurosensories hearing loss

Introduction: To evaluate the otoacustic emissions (EOAETs) in patients with neurosensory hearing loss do not belong to the clinical routine. However it would obtain valuables information concerning the topodiagnosis. Objective: To identify signs of retro cochlear alteration in individuals with neurosensory dysacusis diagnosis. Method: A transversal, observational, quantitative and, prospective study. Were analyzed 34 patients' records of users of the Speech Therapy Attendance Service. In the study were included individuals with neurosensory hearing loss of moderate to deep degree. An evaluation of Passing Otoacustic Emissions (EOAETs) was performed in all the individuals of the sample. Those that do not presented EOAETs had the external and middle ear' condition evaluates through meatoscopy and tympanometry to eliminate ears with sings of conductive alteration. Results: Before that the exclusion criteria were applied, they have remained 13 individuals, totalizing 26 ears: four with hearing loss of moderate degree (15%), four with moderately severe degree (15%), two with severe degree (8%), 15 with deep degree (58%) and, one with deafness (4%). The tympanometric curves found were 22 (85%) Type A and, four (15%) Type C. It was verified the presence of EOAETs in only two ears (8%) of a same individual. Conclusion: It was verified the predominance of the EOAETs absence in individuals with neurosensory hearing loss of moderate to deep degree. In one case the EOAETs were registered, that suggest retrocochlear alteration. Raising suspicion of retrocochlear alterations

The neuronal monoamine transporter VMAT2 is regulated by the trimeric GTPase Go(2

Monoamines such as noradrenaline and serotonin are stored in secretory vesicles and released by exocytosis. Two related monoamine transporters, VMAT1 and VMAT2, mediate vesicular transmitter uptake. Previously we have reported that in the rat pheochromocytoma cell line PC 12 VMAT1, localized to peptide-containing secretory granules, is controlled by the heterotrimeric G-protein Go 2. We now show that in BON cells, a human serotonergic neuroendocrine cell line derived from a pancreatic tumor expressing both transporters on large, densecore vesicles, VMAT2 is even more sensitive to G-protein regulation than VMAT1. The activity of both transporters is only downregulated by G�o 2, whereas comparable concentrations of G�o 1 are without effect. In serotonergic raphe neurons in primary culture VMAT2 is also downregulated by pertussis toxin-sensitive Go 2. By electron microscopic analysis from prefronta

Characterization of a Functional Promoter Polymorphism of the Human Tryptophan Hydroxylase 2 Gene in Serotonergic Raphe Neurons.

Background Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in brain serotonin (5-HT) biosynthesis. Although dysfunction of 5-HT neurotransmission has been implicated in a variety of neuropsychiatric conditions, the human TPH2 promoter has not been characterized in vitro. Methods The functional relevance of TPH2 promoter polymorphisms was determined with luciferase assays in primary serotonergic neurons from rat raphe nuclei and in human small cell lung carcinoma cells (SHP-77 cells). We also investigated transcription factor binding to the variant promoter sequence with electrophoretic mobility shift assay (EMSA). Results The polymorphism rs11178997 of the human TPH2 promoter significantly reduced TPH2 transcriptional activity by 22% and 7% in primary serotonergic neurons and in SHP-77 cells, respectively. In contrast, no significant differences in promoter activity were observed for the G- and T-alleles of rs4570625. The EMSA revealed reduced binding of the transcription factor POU3F2 (also known as Brn-2, N-Oct-3) to the A-allele of the polymorphism rs11178997. Overexpression of POU3F2 resulted in a robust activation of the TPH2 promoter (2.7-fold). Conclusions Our data suggest that the human TPH2 promoter polymorphism rs11178997 impacts on gene expression, which might have implications for the development and function of the serotonergic system in the brain