Verapamil Inhibits Ser202/Thr205 Phosphorylation of Tau by Blocking TXNIP/ROS/p38 MAPK Pathway.

Purpose: Oxidative stress is a hallmark of Alzheimer's Disease (AD) and promotes tau phosphorylation. Since Thioredoxin Interacting protein (TXNIP), the inhibitor of the anti-oxidant system of Thioredoxin, is up regulated in the hippocampus of AD patients, we investigated whether TXNIP plays a role in promoting tau phosphorylation and whether Verapamil, an inhibitor of TXNIP expression, prevents TXNIP downstream effects.

Methods: We analyzed TXNIP expression and tau phosphorylation in the hippocampus of the 5xFAD mice in the absence and presence of a pharmacological treatment with Verapamil.

Evaluation of virus-specific cellular immune response in transplant patients.

Virus-specific immune responses have a major impact on the outcome of the infection. Viral agents that are characterized by latency, such as herpesviruses and polyomaviruses, require a continuous immune control to reduce the extent of viral reactivation, as viral clearance cannot be accomplished, independently from the anti-viral treatment. In transplant patients, morbidity and mortality related to viral infections are significantly increased.

Polyomavirus-associated nephropathy.

Polyomaviruses BK and JC are ubiquitous viruses with high seroprevalence rates in general population. Following primary infection, polyomaviruses BK and JC persist latently in different sites, particularly in the reno-urinary tract. Reactivation from latency may occur in normal subjects with asymptomatic viruria, while it can be associated to nephropathy (PVAN) in kidney transplantat recipients.

Detection of human cytomegalovirus in transbronchial biopsies from lung transplant recipients.

The role of human cytomegalovirus (HCMV) in lung transplantation (LT) and drawbacks related to viral quantification in bronchoalveolar lavage (BAL) underline the potential usefulness of investigating other specimens. Thirty-three LT recipients were prospectively studied by HCMV quantitative real time PCR on matched transbronchial biopsy (TBB), BAL, and whole blood specimens. Overall, 27/33 patients turned out HCMV-positive in at least one specimen: 7.

Clinical impact of HSV-1 detection in the lower respiratory tract from hospitalized adult patients.

The occurrence and clinical impact of herpes simplex virus (HSV) were evaluated in 342 bronchoalveolar lavage specimens from 237 patients. HSV-1 and HSV-2 were detected in 32.1% and <1% of patients, respectively.

Alternative molecular tests for virological diagnosis.

Several nucleic acid amplification techniques (NAATs), particularly PCR and real-time PCR, are currently used in the routine clinical laboratories. Such approaches have allowed rapid diagnosis with a high degree of sensitivity and specificity. However, conventional PCR methods have several intrinsic disadvantages such as the requirement for temperature cycling apparatus, and sophisticated and costly analytical equipments.

In vitro CMV-infection model in fresh and glycerolized skin graft.

Viral infections, especially cytomegalovirus (CMV), are a cause of death in burned patients. Aim of this study was to perform an in vitro CMV-infection model comparing fresh and glycerol-treated fibroblasts and keratinocytes. Cells were plated in plates for the two conditions.

The laboratory of clinical virology in monitoring patients undergoing monoclonal antibody therapy.

The relevant efficacy of monoclonal antibodies (mAbs) has resulted in the successful treatment of several diseases, although susceptibility to infections remains a major problem. This review summarizes aspects of the literature regarding viral infections and mAbs, specifically addressing the risk of infection/reactivation, the measures that can reduce this risk, and the role played by the laboratory of clinical virology in monitoring patients undergoing mAb therapy.

Detection of Mimivirus in bronchoalveolar lavage of ventilated and nonventilated patients.

Background/aims: We investigated the prevalence of Mimivirus in bronchoalveolar lavage (BAL) specimens from ventilated versus nonventilated patients.

Methods: The occurrence of Mimivirus DNA was evaluated by two previously developed real-time PCR assays in 69 BAL specimens: 30 from patients on mechanical ventilation for at least 48 h and 39 from nonventilated patients from different clinical settings, including lung transplant recipients.

Results: None of the BAL specimens from ventilated and nonventilated patients resulted positive for Mimivirus.

Quantitative detection of HHV-6 and HHV-7 in transbronchial biopsies from lung transplant recipients.

The occurrence and significance of HHV-6 and HHV-7 were investigated in pulmonary tissue from lung transplant recipients. Eighty-seven transbronchial biopsies from 30 patients were studied by quantitative real-time PCR; the association with histopathological features was investigated. HHV-6 and HHV-7-DNA were detected in 6.

Development of a quantitative real-time nucleic acid sequence-based amplification assay with an internal control using molecular beacon probes for selective and sensitive detection of human rhinovirus serotypes.

Evidence demonstrating that human rhinovirus (HRV) disease is not exclusively limited to the upper airways and may cause lower respiratory complications, together with the frequency of HRV infections and the increasing number of immunocompromised patients underline the need for rapid and accurate diagnosis of HRV infections. In this study, we developed the first quantitative real-time nucleic acid sequence-based amplification assay with an internal control using molecular beacon probes for selective and sensitive detection of human rhinovirus serotypes. We described a simple method to accurately quantify RNA target by computing the time to positivity (TTP) values for HRV RNA.

Combined measurement of serum DNA and urine VP1 messenger RNA in monitoring BK virus replication in kidney graft recipients.

Evaluation of BK virus replication is a fundamental tool in the monitoring of renal transplant recipients. Herein, we investigated the role of urine VP1 messenger RNA (mRNA) quantification and combined measurement of serum DNA and urine VP1 mRNA in 428 kidney allograft recipients. BK viremia and viruria were detected in 24 (5.

Human cytomegalovirus glycoprotein B genotyping from bronchoalveolar lavage specimens.

The genes encoding glycoprotein complexes of human cytomegalovirus are often polymorphic; in particular, glycoprotein B (gB), which is essential for both in vivo and in vitro replication, is encoded by the highly polymorphic gene UL55. In this study, the distribution of gB genotypes was investigated in 44 bronchoalveolar lavage specimens from adult patients positive for human cytomegalovirus DNA by a multiplex nested fast PCR able to amplify 5 gB genotypes (gB1-gB5). The distribution of gB genotypes was as follows: 12 (27.

Detection of human rhinoviruses in the lower respiratory tract of lung transplant recipients.

The occurrence of human rhinoviruses (HRV) and its relationship to clinical and histopathological findings were investigated in 127 bronchoalveolar lavage specimens from 36 lung transplant recipients by real-time RT-PCR. In addition, 286 samples from 235 other immunocompromised and immunocompetent patients were also studied. HRV was detected in 41.

Genotyping of polyomavirus BK by Real Time PCR for VP1 gene.

Polyomavirus BK latently persist in different sites, including the renourinary tract, and may reactivate causing nephropathy in renal transplant recipients or hemorrhagic cystitis in bone marrow recipients. Based on the sequence of the VP1 gene, four genotypes have been described, corresponding to the four serologically differentiated subtypes I-IV, with different prevalence and geographic distribution. In this study, the development and clinical validation of four different Real-Time PCR assays for the detection and discrimination of BKV genotypes as a substitute of DNA sequencing are described.

Unsuitability of exhaled breath condensate for the detection of herpesviruses DNA in the respiratory tract.

Exhaled breath condensate is a non-invasive method for detecting a wide number of molecules as well as genomic DNA in the airways. No study investigated the detection of viral DNA in exhaled breath condensate, while only one study excluded its usefulness for detection of influenza virus RNA. In this study, the suitability of exhaled breath condensate for detecting herpesviruses infection or reactivation in the respiratory tract of lung transplant recipients was evaluated.

Improvement of HRV quantification using cRNA-based standards for real time RT-PCR.

Real Time RT-PCR developed in recent years represents an useful tool in the diagnosis of RNA viruses. In order to accurately quantify and normalize a RNA target, efficiency of reverse-transcription must be considered. In this study, a cRNA-standard-based quantitative Real Time RT-PCR have been developed for HRV quantification on bronchoalveolar lavage (BAL) specimens.

Human cytomegalovirus load in fresh and glycerolized skin grafts.

This study evaluated the detection of Human Cytomegalovirus (HCMV)-DNA in donors' skin samples. HCMV-DNA was quantified in 100 skin specimens, including 50 fresh samples and as many corresponding glycerol-preserved specimens by a home-made Real Time PCR. HCMV-DNA was detected in 19/50 (38%) fresh specimens and 23/50 (46%) glycerol-preserved (p = n.

Quantitative detection of the new polyomaviruses KI, WU and Merkel cell virus in transbronchial biopsies from lung transplant recipients.

Background: Recently, three new polyomaviruses-KI, WU and Merkel cell (MCV)-have been discovered and their detection has been reported in different types of specimens, including respiratory samples, suggesting their shedding in the airways. In lung graft recipients, viral agents are associated with events that may limit the success of transplantation, including organ infection/disease and allograft rejection.

Aims: To evaluate the prevalence of KI, WU and MCV in transbronchial biopsies from lung transplant recipients and investigate the association with clinical and histopathological features.

Real-time RT-PCR assay for the quantitation of polyomavirus BK VP1 mRNA levels in urine.

In renal transplant recipients, polyomavirus BK can reactivate resulting in graft nephropathy. Screening for BK virus replication may allow for earlier interventions with reduced allograft loss. The measurement of urinary cell BKV VP1 mRNA for identify viral replication levels at risk of developing nephropathy has been proposed.

Detection of human herpesvirus-7 DNA in bronchoalveolar lavage.

Objectives: Human herpesvirus-7 (HHV-7) is a highly seroprevalent virus that, following primary infection, establishes latency or persistence in some tissues, including lung. The aim of this study was to investigate the prevalence of HHV-7 in the lower respiratory tract of hospitalized adult patients.

Methods: The prevalence of HHV-7 DNA was determined by quantitative real-time PCR in 212 bronchoalveolar lavage (BAL) samples obtained from 153 patients.

Detection of parvovirus B19 in the lower respiratory tract.

Background: Human parvovirus B19 infection generally displays a self-limiting course followed by viral clearance; although, in some cases, persistent infection may occur. Few cases of severe pulmonary disease following primary infection in both immunocompetent and immunocompromised patients were reported.

Objectives: To investigate the prevalence and clinical impact of parvovirus B19 in the lower respiratory tract.