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Revista de diagnóstico y biomarcadores moleculares

Volumen 7, Asunto 2 (2016)

Artículo de investigación

Biomarkers in Neurodegenerative Diseases: Cortisol

Patrícia Batista and Anabela Pereira

Neurodegenerative diseases are characterized by progressive loss of cognitive function, dementia, and problems with movements.

Identification of biomarkers during disease process, induce to an effective and early diagnostic test for neurodegenerative diseases. These biomarkers would allow presymptomatic disease detection of disease and would be valuable for monitoring the efficacy of disease.

Cortisol is a biomarker used for stress evaluation and a potential neurodegenerative disease biomarker.

Objective: The aim of this paper is to review systematically the scientific literature about evaluation to cortisol biomarker in neurodegenerative diseases.

Methods: Systematic literature review on Pubmed, Medline and Scopus database with the keywords "cortisol biomarkers” and "neurodegenerative diseases". It was analyzed all existing articles (between 1988 and 2015). PRISMA criteria reporting of systematic reviews and meta-analyses were applied. The inclusion criteria were: cortisol biomarkers in neurodegenerative diseases diagnosis, presenting quantitative or qualitative results. It was excluded articles outside the scope of the subject and articles with unavailable information.

Results: After applying the methodology, 14 scientific articles were included in the study. So, these studies were analyzed. Conclusions: This paper review based on the contribution of cortisol biomarkers to diagnose and treat neurodegenerative diseases.

Artículo de investigación

Oct2, BCL6, IRF8, OCAB and PU.1 in the Assessment of Prognosis in Diffuse Large B cell Lymphoma Patients

Rojas-Bilbao EA, Knott ME, Bal de Kier Joffé ED, Zerga ME, Nuñez M, Puricelli LI and Ranuncolo SM*

Background: Diffuse Large B-Cell Lymphoma (DLBCL) is the most common type of Non-Hodgkin Lymphoma in adults. This germinal center derived B cell lymphoma is a heterogeneous disease with a highly variable clinical course, currently treated with immune-chemotherapy. The International Prognosis Index (IPI) remains the main prognosis indicator. This highlights the absence of biomarkers suitable to provide molecular biology information to more accurately establish prognosis and predict treatment response in DLBCL patients.

Methods: We determined the Oct2, BCL6, IRF8, OCAB and PU.1 transcription factors expression by immunohistochemistry in 73 DLBCL lymph node biopsies to address their potential as prognosis biomarkers in DLBCL patients. These molecules exhibit well-known key roles in the germinal center development.

Results: A large number of cases showed high Oct2 (64/73), BCL6 (40/73) and/or IRF8 (44/73) percentage of positive tumor cell nuclei. In contrast, a significant number of analyzed biopsies, showed a low OCAB and/or PU.1 percentage of positive tumor cells. The expression of each factor was not associated with any of the relevant clinical-pathological features including the DLBCL molecular subtype and the IPI. Oct2, BCL6 and IRF8 high expression (more than 70% of positive tumor cells) correlated with poor prognosis in terms of shorter overall survival. Particularly, high BCL6 and IRF8 expression maintained their prognostic value in a multivariate analysis stratified for the IPI score. Interestingly, IRF8 emerged as a novel prognosis indicator among the free bone marrow disease patients at diagnosis, subjected to a specific multivariate analysis named classification tree. Patients with free-bone marrow disease, which normally have a better outcome, showed a worse prognosis when they expressed high IRF8 at diagnosis.

Conclusions: The assessment of these factors expression would provide novel cellular and molecular insights to more efficiently predict DLBCL patient prognosis.

Artículo de investigación

Anti-diabetic Activities of the Fruit Aegle mamelos

Repon kumer Saha, Arfatoon Nesa, Kamrun Nahar and Mahfuja Akter

Objective: The objective of this study is pharmacological activities investigation of Aegle marmelos fruit.

Methods: After getting the sample (fruit) as dried powder, some sample was used for lactin isolation by ammonium sulphate precipitation method and some were used for methanolic extraction. Vacuum liquid chromatography (VLC), Thin layer chromatography (TLC) were used to detect the presence of various types of compound in rind. Presence of carbohydrate and proteins were investigated by thin layer chromatography. In vitro anti-diabetic assay was carried out by glucose uptake in yeast cells. Disc diffusion assay was performed to show the antibacterial effect using gram positive and gram negative strains of bacteria.

Result: Two extracts were used. One was methanolic extract and another was lectin extract. VLC fraction of methanolic extract of the Aegle marmelos fruit contains flavonoids and other biologically active compounds. The extract showed antibacterial activities against several bacteria. The lectin extract also showed antibacterial and anti-diabetic activity.

Conclusion: Therefore, Aegle marmelos may be considered as a plant of various health benefits.

Artículo de revisión

IL-3 Receptor Alpha Chain is a Biomarker and a Therapeutic Target of Myeloid Neoplasms

Ugo Testa, Germana Castelli and Elvira Pelosi

The alpha-chain of the interleukin-3 receptor (IL-3RA or CD123) is frequently deregulated in myeloid neoplasias and its deregulation contributes to survival and proliferation of malignant cells. This review is focused to the analysis of the diseases in which CD123 is markedly overexpressed, such as blastic plasmocytoid dendritic neoplasms (BPDCN), systemic mastocytosis (SM), chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). The highly overexpressed IL-3R represents also a molecular target suitable for the development of specific targeted therapies using either the IL-3 ligand fused with cytotoxic drugs, or mono-, bi- or tri-specific anti-CD123 monoclonal antibodies or CD123-specific chimeric antigen receptor T cells.

Artículo de investigación

The Utility of Automated HCV Core Antigen Assay as an Alternative to PCR in Chronic HCV Egyptian Patients

Ehab M Abd El-reheem, Magdy Fouad, Hanaa Kh Fath El-bab and Waleed M Abd El-Hmeed

Hepatitis C is a disease with a significant global impact. Although the detection and quantitation of HCV RNA have been the standard method for the diagnosis and assessing individual patient response to the antiviral drug regimen, it is very sensitive testing, expensive, labor intensive, and requires technical skill.

Since the HCV core Ag assay is easy to perform in an immunoassay format, cheap, and less prone to sample carryover contamination compared to nucleic acid tests, There is an increasing interest to use HCV core antigen as a reflex test for seropositive individual to identify the active HCV infection also can be used to detect the early HCV infection.

Aim of the work: To compare the diagnostic accuracy of HCV core antigen with HCV-PCR in chronic HCV Egyptian patients.

Patients and methods: HCV core Ag was measured by a fully automated chemiluminescent immunoassay (CLIA) ABBOTT diagnostics in 57 patients proven to be chronic hepatitis C from those 32 were treated with pegylated interferon and ribavirin therpay and achieved HCV RNA negative six monthes after stoppage of treatment ( successful SVR) and 25 chronic HCV patients not considered for treatment . Viral load was quantified with branched DNA (bDNA, Versant, Siemens) also sera were tested with the Architect HCV Ag test (Abbott Laboratories). Statistical analysis was performed on logarithmically transformed values.

Results: HCV core antigen was detectable in 19/25 and grey zone in 4/25 HCV RNA positive sera while 2 sera were negative for HCV Ag. HCV-Ag was undetectable in all 32 HCV RNA negative samples. The sample with the lowest viral load that tested positive for HCV-Ag contained 1200 IU/mL HCV RNA. The levels of HCV core antigen showed a good correlation with those from the HCV RNA quantification (r = 0.907) HCV core Ag levels were correlated significantly with ALT levels (r = 0.516; P < 0.0001)

Conclusion: In conclusion, the Architect HCV antigen assay is highly sensitive, (>90%) reliable, easy to perform, cost-effective, and applicable as a screening, supplemental, and preconfirmatory test for anti-HCV assays used in laboratory procedures for the diagnosis of hepatitis C virus infection.

Artículo de investigación

Single Base Primer Extension Assay (SNaPshot) for Rapid Detection of Human Immunodeficiency Virus - 1 Drug Resistance Mutations

Arpan A, Salil V, Harsh P and Pratap NM

The 3' primer extension assay can be employed to interrogate multiple known single nucleotide polymorphisms (SNPs) simultaneously using a multiplex approach. Over 200 Human Immunodeficiency Virus-1 (HIV-1) mutations are currently associated with drug resistance. Identifying these mutations assist in taking appropriate therapeutic decisions such that superior drug regimens can be designed for keeping the viral load below pathogenic level. Presently, reverse transcription of HIV-1 RNA followed by amplification of the pol gene and subsequent nucleotide sequencing is a popular method of HIV-1 drug resistance genotyping. However, it is still a time consuming and laborious protocol and require significant bioinformatics analysis in order to decipher the significance of mutations encountered during analysis.

In this study we analyzed 75 HIV-1 positive clinical samples for 2 representative mutations, viz., M41L and M184V using a 3' primer extension protocol popularly known as SNaPshot assay. Twenty four and 36% of the patients were found to harbor the critical M41L and M184V mutations respectively while 20% were found to contain both the mutations together. The results were 100% concordant with DNA sequencing assay which was used as a gold standard. The results substantiate the cost, speed and economy-related advantages of this technology platform for interrogating known mutations of significance within the HIV-1 genome.

Artículo de investigación

Evidence of Hepatitis C Virus Infection and Associated Treatment in Nepal

Akriti Nepal and Bimal Kunwar

Hepatitis C, a liver disease caused by the hepatitis C virus can be acute and chronic infection. Most of the studies conducted in Nepal are focused on the prevalence of hepatitis C Virus. It detects active disease only but does not detect the infections of the past which became immune naturally. The present study hence was conducted to determine the prevalence and the epidemiological characteristics of Hepatitis C. The research was carried out in Sukraraj Tropical and Infectious Disease Hospital/Teku Hospital, Kathmandu, Nepal. The prevalence of hepatitis C virus (HCV) infection was 2700 number of HIV infection patients. An Analysis was conducted, and included calculation of hepatitis C infection by each variable of interest, including sex, age, profession, marital status, history of jaundice by the patient, invasive procedure, and history of blood transfusion and providing medicines and liver biopsy test. The result showed that there was a low frequency of HCV in all the patients infected with HIV. In Teku Hospital, 100 among 2700 patients were infected with hepatitis C (3.703%). This suggests that preventive measures for this disease can improve the situation significantly.

Presently, Teku Hospital uses antiviral drugs, vitamin complexes and common Anti-inflammatory, Anti-pyretic drugs to provide immediate relief to the patients. But in absence of interferon in the treatment, the patients don’t get proper respite. For betterment of the situation, interferons like (Pegylated Interferon) and Ribavirin should be included in the list of essential drugs in Nepal, along with implementation of proper preventive measures against HCV.

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