Clinical Use of -2proPSA (p2PSA) and Its Derivatives (%p2PSA and Prostate Health Index) for the Detection of Prostate Cancer: A Review of the Literature

Prostate-specific antigen (PSA) is recognized as an organ-specific marker with low specificity and sensitivity in discriminating prostate cancer (PCa) from other benign conditions, such as prostatic hyperplasia or chronic prostatitis. Thus, in the case of clinical suspicion, a PCa diagnosis cannot be made without a prostate biopsy. [-2]proPSA (p2PSA), a precursor of PSA, has been investigated as a new marker to accurately detect PCa. The aim of this systematic review was to discuss the available literature regarding the clinical validity and utility of p2PSA and its derivatives, p2PSA/fPSA (%p2PSA) and the Prostate Health Index (PHI). A systematic search of the PubMed and Scopus electronic databases was performed in accordance with the PRISMA statement (http://www.prisma-statement.org), considering the time period from January 1990 to January 2014 and using the following search terms: proprostate specific antigen, proenzyme PSA, proPSA, [-2]proPSA, p2PSA, Prostate Health Index, and PHI. To date, 115 studies have been published, but only 35 were considered for the qualitative analysis. These studies suggested that p2PSA is the most cancer-specific form of PSA, being preferentially expressed in PCa tissue and being significantly elevated in the serum of men with PCa. It is now evident that p2PSA, %p2PSA, and PHI measurements improve the specificity of the available tests (PSA and derivatives) in detecting PCa. Moreover, increasing PHI values seem to correlate with more aggressive disease. Some studies have compared p2PSA and its derivatives with other new biomarkers and found p2PSA to be significantly more accurate. Indeed, the implementation of these tests in clinical practice has the potential to significantly increase the physician's ability to detect PCa and avoid unnecessary biopsies, while also having an effective impact on costs. Further studies in large, multicenter, prospective trials are required to confirm these encouraging results on the clinical utility of these new biomarkers.

Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis

Because histopathological changes in the lungs of patients with systemic sclerosis (SSc) are consistent with alveolar and vessel cell damage, we presume that this interaction can be characterized by analyzing the expression of proteins regulating nitric oxide (NO) and plasminogen activator inhibitor-1 (PAI-1) synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and other clinical data, we studied these markers in 23 cases of SSc nonspecific interstitial pneumonia (SSc-NSIP). We used immunohistochemistry and morphometry to evaluate the amount of cells in alveolar septa and vessels staining for NO synthase (NOS) and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP, pulmonary function tests, and survival time until death. General linear model analysis demonstrated that staining for septal inducible NOS (iNOS) related significantly to staining of septal cells for interleukin (IL)-4 and to septal IL-13. In univariate analysis, higher levels of septal and vascular cells staining for iNOS were associated with a smaller percentage of septal and vascular cells expressing fibroblast growth factor and myofibroblast proliferation, respectively. Multivariate Cox model analysis demonstrated that, after controlling for SSc-NSIP histological patterns, just three variables were significantly associated with survival time: septal iNOS (P=0.04), septal IL-13 (P=0.03), and septal basic fibroblast growth factor (bFGF; P=0.02). Augmented NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4 staining in alveolar septa and vessels provides a possible independent diagnostic measure for the degree of pulmonary dysfunction and fibrosis with an impact on the survival of patients with SSc.

Detección de ADN de Chlamydophila Pneumoniae en líquido cefalorraquídeo proveniente de pacientes diagnósticados con enfermedad de alzheimer / DNA detection of chlamydophila Pneumoniae in cerebrospinal fluid of patients diagnosed with alzheimer disease

La enfermedad de alzheimer (EA) es un desorden neurodegenerativo y la isoforma 4 de apolipoproteína E (ApoE) es mundialmente aceptada como un factor de riesgo para el desarrollo de alzheimer esporádico. La EA se ha asociado con infecciones por Chlamydophila pneumoniae (ChP) debido a que inhibe la respuesta inmune del huésped generando infecciones crónicas. El objetivo fue detectar el ADN de ChP en líquido cefalorraquídeo (LCR) de pacientes con diagnóstico clínico de alzheimer provenientes de distrito metropolitano de caracas. Se analizaron (7) muestras de LCR de pacientes con diagnóstico clínico de EA y el grupo control estuvo constituido por (13) muestras de LCR de pacientes con otras enfermedades neurológicas (OND) no demencia. A los cuales se les determino la isoforma de ApoE, se amplificaron los genes para OmcA y 16Sribosomal de ChP. La frecuencia de apoE isoforma 4 en los pacientes con EA fue (0,57) en contrste con el grupo control donde la frecuencia fue de (0,31). En todas las mustras analizadas se obtuvo una ausencia de la banda correspondiente a Chlamydophila pneumoniae. La mayor probabilidad es que la bacteria no se encontrara en el LCR de los pacientes. Pero existe la posibilidad de que ADN de ChP no estuviese en suficiente cantidad como para ser detectado por las técnicas empleadas. Además, debemos considerar que el protocolo de extracción es un punto crítico. Finalmente, los pacientes con diagnóstico clínico de EA y en particular del género femenino tienen mayor frecuencia de tener una copia de ApoE isoforma 4 en su genotipo.

Alzheimer's disease (AD) is a neurodegenerative disorder and the isoform 4 of apoliporotein E (ApoE) is world accepted as a risk factor for developing sporadic alzheimer. The AD has been associated with infections by Chlamydophila pneumoniae (ChP) because it inhibits the host immune response causing chroic infections. To detected ChP DNA in cerebrospinal fluid (CSF) of patients with clinical diagnosis lf alzheimer's from the metropolitan district of caracas. We analyzed (7) CSF samples from patients with clinical diagnsis of AD and control groups consisted of (13) CSF samples from patientes with other neurological diseases (OND) no dementia. To with the determined the isoform of ApoE genes were amplified for OmcA and 16Sribosomal of ChP. The frecuency of ApoE isoform 4 in AD patients was (0.57) in contrast to the control group where the frequency was (0.31). All samples were obtained an absence of the band corresponding to Chlamydophila pneumoniae. The greater likelihood is that the bacteria is not found in the CSF of patients. But there is the possibility that DNA was no ChP insufficient quantity to be detected by the techniques employed. Furthermore, we most consider the extraction protocol is a critical point. Finally, patients with clinical diagnosis of Ad and in particular the female are more often have a copy of ApoE isoform 4 in its genotype.