Efficacy and safety of prostate vaporesection using a 120-W 2-μm continuous-wave Tm:YAG laser (RevoLix 2) in patients on continuous oral anticoagulant or antiplatelet therapy

The aim of our current study was to demonstrate the efficacy and safety of vaporesection using a 120-W Tm:YAG laser (Revolix Duo) in patients with BPH receiving systemic anticoagulation or antiplatelet therapy. Between April 2010 and November 2011, a total of 76 patients using oral antiplatelet or anticoagulant (OA) agents affected by LUTS for BPH were underwent thulium vaporesection of the prostate (ThuVARP) using a 120-W 2-μm CW Tm:YAG laser and evaluated at 3- and 6-month follow-up. Of these, in 41 patients (group A) was performed vaporesection while receiving OA therapy. In 35 patients (group B), OA agents were discontinued 10 days before surgery. There were no significant differences in average vaporesection times, catheterization time, or hospital stay. There was no significant change in serum sodium level before and immediately after vaporesection in either group. Significant improvements compared to baseline were observed at each postoperative assessment in both groups for Qmax, PVR, IPSS, and QoL. More specifically, the IPSS score improved from 21.7 at baseline to 5.2 at 6 months in group A and from 20.7 to 4.5 in group B. At 6 months, Qmax increased 226 and 190 % for the 2 groups, respectively. The PVR decreased from 119 at baseline to 11 mL at 6 months in group A and from 125 to 11 mL in group B. ThuVARP is a safe and efficient procedure for patients with BPH, refractory to pharmacotherapy, who require active antiplatelet or anticoagulant therapy.     

Orthodontic anomalies and malocclusions in Late Antique and Early Mediaeval period in Croatia

ObjectiveMalocclusions are relative infrequently analysed in bioarchaeological investigations and if investigated the samples are very small. This research provides analysis of orthodontic anomalies of even 1118 individuals from the Late Antique (LA) and Early Mediaeval (EM) period. Aims were to describe the prevalence of orthodontic anomalies in this historical period and to analyse which orthodontic anomalies are best suitable for bioarchaeological investigations.Methods1118 skulls were examined for anomalies of tooth number, tooth displacement (rotation, malposition, diastema and crowding) as well as for malocclusions.ResultsThe prevalence of hypodontia in the LA was 41.02% and 30.61% in the EM sample. Tooth displacement was noticed in 15.63% individuals from the LA and in 12.42% individuals from EM. About 26% of the LA sample and 7.19% of the EM sample were affected with tooth crowding and the difference was statistically significant.ConclusionOrthodontic anomalies affecting only one tooth or group of teeth are more suitable for examination in bioarchaeological investigations than orthodontic features requiring presence of both jaws and all or almost all teeth. Clinical investigation protocols and methodology should be adopted for bioarchaeological researches and international standards and recommendations should be established for this kind of investigation on skeletal remains.     

Survey of the temporal changes in HIV-1 replicative fitness in the Amsterdam Cohort

Changes in virulence and fitness during an epidemic are common among pathogens. Several studies have shown that HIV fitness increases within a patient during disease progression, while bottlenecks, such as sexual transmission, immune pressure and drug treatment can reduce fitness. In this study, we analyzed how these opposing forces have shaped HIV-1 fitness over time. Therefore, we compared the replicative fitness of HIV-1 isolates from newly infected untreated individuals, diagnosed for HIV-1 infection early in the AIDS epidemic in Amsterdam, the Netherlands, with more recent isolates. Twenty-five early and late HIV-1 isolates, carefully matched for seroconversion time, were competed head-to-head in a dual infection/competition assay, employing peripheral blood mononuclear cells. In contrast with previous studies, we observed a trend of increasing fitness over time in the HIV epidemic of Amsterdam. Apparently, the bottleneck, occurring with each transmission event, does not completely reset the fitness increase acquired during disease progression.     

Roles of PCNA-binding and ubiquitin-binding domains in human DNA polymerase η in translesion DNA synthesis

Treatment of yeast and human cells with DNA-damaging agents elicits Rad6–Rad18-mediated monoubiquitination of proliferating cell nuclear antigen (PCNA) at its Lys-164 residue [ubiquitin (Ub)-PCNA], and this PCNA modification is indispensable for promoting the access of translesion synthesis (TLS) polymerases (Pols) to PCNA. However, the means by which K164-linked Ub modulates the proficiency of TLS Pols to bind PCNA and take over synthesis from the replicative Pol has remained unclear. One model that has gained considerable credence is that the TLS Pols bind PCNA at 2 sites, to the interdomain connector loop via their PCNA-interacting protein (PIP) domain and to the K164-linked Ub moiety via their Ub-binding domain (UBD). Specifically, this model postulates that the UBD-mediated binding of TLS Pols to the Ub moiety on PCNA is necessary for TLS. To test the validity of this model, we examine the contributions that the PIP and Ub-binding zinc finger (UBZ) domains of human Polη make to its functional interaction with PCNA, its colocalization with PCNA in replication foci, and its role in TLS in vivo. We conclude from these studies that the binding to PCNA via its PIP domain is a prerequisite for Polη''s ability to function in TLS in human cells and that the direct binding of the Ub moiety on PCNA via its UBZ domain is not required. We discuss the possible role of the Ub moiety on PCNA in TLS.     

Diltiazem and/or desferrioxamine administered at the time of reperfusion fail to improve post-ischemic recovery in the isolated rat heart after long-term hypothermic storage

The ability of diltiazem and/or desferrioxamine to enhance the recovery of cardiac contractile function during reperfusion after prolonged hypothermic storage was assessed. Isolated rat hearts were arrested with St. Thomas' Hospital Cardioplegic Solution and stored for 10 h at 4 degrees C. Reperfusion in the Langendorff mode was initially carried out with crystalloid perfusate with or without added diltiazem (0.5 mumol/l) and/or desferrioxamine (15, 50, 100, 150 or 250 mumol/l). After 15 min the drugs were discontinued and the hearts were perfused for a further 45 min. Diltiazem reduced leakage of creatine (CK) kinase during the first 15 min of reperfusion from 102 +/- 8 IU/15 min/g dry wt to 67 +/- 9 IU/15 min/g dry wt (P less than 0.05). However, during the subsequent period of diltiazem-free perfusion, CK leakage was similar to control values (131 +/- 24 vs 142 +/- 34 IU/45 min/g dry wt, respectively). After 1 h of reperfusion there was no significant difference in total CK leakage between the diltiazem and the control groups (198 +/- 32 vs 244 +/- 39 IU/60 min/g dry wt, respectively). Desferrioxamine had no effect on CK leakage at any of the doses studied. Diltiazem significantly reduced leakage of enzyme during the initial reperfusion phase when combined with desferrioxamine; however, as with diltiazem alone, this protection was lost after the drug was withdrawn. Post-ischemic contents of adenosine triphosphate and creatine phosphate were similar in all groups as was the final recovery of function, as assessed by left ventricular developed pressure at an end-diastolic pressure of 5 mmHg. In conclusion, neither diltiazem nor desferrioxamine nor both together could be shown to confer benefit during reperfusion after long-term storage.     

Angiotensin Receptor Type 2 Activation Induces Neuroprotection and Neurogenesis After Traumatic Brain Injury

Angiotensin II receptor type 2 (AT₂) agonists have been shown to limit brain ischemic insult and to improve its outcome. The activation of AT₂ was also linked to induced neuronal proliferation and differentiation in vitro. In this study, we examined the therapeutic potential of AT₂ activation following traumatic brain injury (TBI) in mice, a brain pathology that displays ischemia-like secondary damages. The AT₂ agonist CGP42112A was continuously infused immediately after closed head injury (CHI) for 3 days. We have followed the functional recovery of the injured mice for 35 days post-CHI, and evaluated cognitive function, lesion volume, molecular signaling, and neurogenesis at different time points after the impact. We found dose-dependent improvement in functional recovery and cognitive performance after CGP42112A treatment that was accompanied by reduced lesion volume and induced neurogenesis in the neurogenic niches of the brain and also in the injury region. At the cellular/molecular level, CGP42112A induced early activation of neuroprotective kinases protein kinase B (Akt) and extracellular-regulated kinases ½ (ERK½), and the neurotrophins nerve growth factor and brain-derived neurotrophic factor; all were blocked by treatment with the AT₂ antagonist PD123319. Our results suggest that AT₂ activation after TBI promotes neuroprotection and neurogenesis, and may be a novel approach for the development of new drugs to treat victims of TBI.