Adriana Antônia da Cruz Furini

Detection of Mycobacterium tuberculosis complex by nested polymerase chain reaction in pulmonary and extrapulmonary specimens

OBJECTIVE: To compare the performance of nested polymerase chain reaction (NPCR) with that of cultures in the detection of the Mycobacterium tuberculosis complex in pulmonary and extrapulmonary specimens. METHODS: We analyzed 20 and 78 pulmonary and extrapulmonary specimens, respectively, of 67 hospitalized patients suspected of having tuberculosis. An automated microbial system was used for the identification of Mycobacterium spp. cultures, and M. tuberculosis IS6110 was used as the target sequence in the NPCR. The kappa statistic was used in order to assess the level of agreement among the results. RESULTS: Among the 67 patients, 6 and 5, respectively, were diagnosed with pulmonary and extrapulmonary tuberculosis, and the NPCR was positive in all of the cases. Among the 98 clinical specimens, smear microscopy, culture, and NPCR were positive in 6.00%, 8.16%, and 13.26%, respectively. Comparing the results of NPCR with those of cultures (the gold standard), we found that NPCR had a sensitivity and specificity of 100% and 83%, respectively, in pulmonary specimens, compared with 83% and 96%, respectively, in extrapulmonary specimens, with good concordance between the tests (kappa, 0.50 and 0.6867, respectively). CONCLUSIONS: Although NPCR proved to be a very useful tool for the detection of M. tuberculosis complex, clinical, epidemiological, and other laboratory data should also be considered in the diagnosis and treatment of pulmonary and extrapulmonary tuberculosis.

Polymorphisms in B Cell Co-Stimulatory Genes Are Associated with IgG Antibody Responses against Blood–Stage Proteins of Plasmodium vivax

The development of an effective immune response can help decrease mortality from malaria and its clinical symptoms. However, this mechanism is complex and has significant inter-individual variation, most likely owing to the genetic contribution of the human host. Therefore, this study aimed to investigate the influence of polymorphisms in genes involved in the costimulation of B-lymphocytes in the naturally acquired humoral immune response against proteins of the asexual stage of Plasmodium vivax. A total of 319 individuals living in an area of malaria transmission in the Brazilian Amazon were genotyped for four SNPs in the genes CD40, CD40L, BLYS and CD86. In addition, IgG antibodies against P. vivax apical membrane antigen 1 (PvAMA–1), Duffy binding protein (PvDBP) and merozoite surface protein 1 (PvMSP–119) were detected by ELISA. The SNP BLYS –871C>T was associated with the frequency of IgG responders to PvAMA–1 and PvMSP–119. The SNP CD40 –1C>T was associated with the IgG response against PvDBP, whereas IgG antibody titers against PvMSP–119 were influenced by the polymorphism CD86 +1057G>A. These data may help to elucidate the immunological aspects of vivax malaria and consequently assist in the design of malaria vaccines.

Opportunistic infections among individuals with HIV-1/AIDS in the highly active antiretroviral therapy era at a Quaternary Level Care Teaching Hospital

INTRODUCTION In this study, clinical-laboratory and epidemiological characteristics are described for a group of 700 individuals with HIV (human immunodeficiency virus)/AIDS (acquired immunodeficiency syndrome) in the ART (antiretroviral therapy) era at a teaching hospital that provides a quaternary level of care, with an emphasis on opportunistic infections (OIs), co-infections and immune profile. METHODS A retrospective cross-sectional study of AIDS cases was conducted from 1998 to 2008 by reviewing medical records from the Base Hospital/FUNFARME (Fundação Faculdade Regional de Medicina), São José do Rio Preto, São Paulo, Brazil. RESULTS The individuals were 14 to 75 years of age, and 458 were males. Heterosexuals accounted for 31.1% of all patients. Eighty-three percent were on ART, and 33.8% of those presented difficulties with treatment adherence. OIs were analyzed from medical records, and Pneumocystis jiroveci pneumonia was the most prevalent, regardless of the LTCD4+ (TCD4+ Lymphocytes) levels. Individuals whose viral loads were ≥10,000 showed a 90% greater chance of neurotoxoplasmosis. For P. jiroveci pneumonia, neurotoxoplasmosis, esophageal candidiasis, pulmonary tuberculosis and neurocryptococcosis, the chances of infection were higher among patients with LTCD4+ levels below 200 cells/mm3. HIV/hepatitis C virus (HCV) and HIV/hepatitis B virus (HBV) co-infections were significantly associated with death. CONCLUSIONS OIs remain frequent in the ART era even in populations where the access to medical care is considered satisfactory.

Humoral immune responses against the malaria vaccine candidate antigen Plasmodium vivax AMA-1 and IL-4 gene polymorphisms in individuals living in an endemic area of the Brazilian Amazon

BACKGROUND Several studies have recently demonstrated that the immune responses against malaria is governed by different factors, including the genetic components of the host. The IL-4 gene appears to be a strong candidate factor because of its role in the regulation of the Th2 response. The present study investigated the role of IL-4 polymorphisms in the development of IgG antibodies against PvAMA-1 and the IL-4 levels in individuals infected with Plasmodium vivax in a malaria endemic area in the Brazilian Amazon. METHODS The study sample included 83 patients who were diagnosed with P. vivax infection using thick smear and confirmed by nested-PCR. The IL-4 -590C>T and IL-4 -33C>T polymorphisms were genotyped by PCR-RFLP, and the intron 3 VNTR was genotyped by PCR. A standardised ELISA protocol was used to measure the total IgG against PvAMA-1. The cytokine/chemokine levels were measured using a Milliplex multiplex assay (Millipore). All of the subjects were genotyped with 48 ancestry informative markers to determine the proportions of African, European and Amerindian ancestry using STRUCTURE software. RESULTS Of the 83 patients, 60 (73%) produced IgG antibodies against PvAMA-1. A significant decrease in the percentage of respondents was observed among the primo-infected individuals. No significant differences were observed in the frequencies of genotypes and haplotypes among individuals who were positive or negative for IgG antibodies against PvAMA-1. Furthermore, no significant correlation was observed between the IL-4 polymorphisms, antibody levels, IL-4 levels, and parasitemia. CONCLUSIONS This study indicated that the polymorphisms identified in the IL-4 gene are not likely to play a role in the regulation of the antibody response against PvAMA-1 and IL-4 production in vivax malaria.

Frequency of TNFA, INFG, and IL10 Gene Polymorphisms and Their Association with Malaria Vivax and Genomic Ancestry

Polymorphisms in cytokine genes can alter the production of these proteins and consequently affect the immune response. The trihybrid heterogeneity of the Brazilian population is characterized as a condition for the use of ancestry informative markers. The objective of this study was to evaluate the frequency of -1031T>C, -308G>A and -238G>A TNFA, +874 A>T IFNG and -819C>T, and -592C>A IL10 gene polymorphisms and their association with malaria vivax and genomic ancestry. Samples from 90 vivax malaria-infected individuals and 51 noninfected individuals from northern Brazil were evaluated. Genotyping was carried out by using ASO-PCR or PCR/RFLP. The genomic ancestry of the individuals was classified using 48 insertion/deletion polymorphism biallelic markers. There were no differences in the proportions of African, European, and Native American ancestry between men and women. No significant association was observed for the allele and genotype frequencies of the 6 SNPs between malaria-infected and noninfected individuals. However, there was a trend toward decreasing the frequency of individuals carrying the TNF-308A allele with the increasing proportion of European ancestry. No ethnic-specific SNPs were identified, and there was no allelic or genotype association with susceptibility or resistance to vivax malaria. Understanding the genomic mechanisms by which ancestry influences this association is critical and requires further study.

Human Interleukin 2 (IL-2) Promotion of Immune Regulation and ClinicalOutcomes: A Review

Interleukin 2 (IL-2) is a monomeric glycoprotein that is primarily produced by activated CD4+ T cells, CD8+ T cells and dendritic cells. It is characterized as a proinflammatory cytokine that is secreted by Th1 cells. IL-2 plays a central role in the activation of regulatory T cells to produce the cytokines tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). IL-2 may also enhance the cytolytic activity of natural killer cells, thereby ensuring their significance in the control of the immune response, and effectively participate in the pathogenesis of several pathological conditions, such as cancer and metabolic, infectious, autoimmune and inflammatory diseases. We emphasize the importance of studies of IL-2 and discuss perspectives resulting from our increasing understanding of genetic diversity and its role in the immune response.

Hereditary predisposition to breast cancer and its relation to the BRCA1 and BRCA2 genes: literature review

Breast cancer is the main cancer that affects the female population in the world, with a higher incidence and mortality rate, and 5 to 10% of all cases are related to the inheritance of genetic mutations. Early identification of cases of breast and ovarian cancer is important as an affected individual may inherit property from a family history indicating a hereditary predisposition. The carcinogenic effect may occur when two major suppressor genes, such as BRCA1 and BRCA2, lose their function in the two alleles due to germline mutations. Thus, a review of the literature on hereditary breast cancer and its correlations with germline mutations in the BRCA1 and BRCA2 genes that increase the risk for the development of breast cancer.

Serum level of prostate specific antigen in users of a clinical laboratory of Novo Horizonte, São Paulo

The Prostate cancer (PCa) is the second cancer diagnosed in adult men and the sixth most common in the world. The Prostate Specific Antigen (PSA) is considered the most important marker to detect, monitor and interning PCa. The increase of this marker is related to age and the dosage recommendation in men over 40 years. The aim of this study was to analyze laboratory data from PSA and epidemiological of 58 patients. A retrospective study from medical record of Analysis Laboratory Health Center Clinics in the city of Novo Horizonte. The most prevalent age was between 61 and 70 years (36.4%), followed by patients aged over 81 years (19.2%) among other less frequent age groups. Seven patients had changes in test results (> 4,0ng / ml), but only one was diagnosed with PCa requiring treatment in specialized hospital. The relationship between the total and free PSA below 15% was detected in three patients, suggesting PCa. The results described in this study allowed us to evaluate the age factor is important, as serum PSA levels increase with age and PCa can be considered as a cancer from third age.

Analysis of potential drug interactions and adverse reactions to nonsteroidal anti-inflammatory drugs among the elderly

Objective: The aim of the present study was to analyze potential drug interactions and adverse reactions to NSAIDs in elderly users of a private drug distribution service. Method: A prospective, exploratory and descriptive study with a quantitative approach was performed. The elderly users of NSAIDs attended by the service were interviewed and their prescriptions analyzed between May and September, 2014. Analysis of drug interactions was performed through computerized databases. The post-sales analysis of adverse reactions was performed using the Adverse Drug Reaction Probability Scale. Statistical analysis was performed with the Chi-squared and Fishers Exact tests. Results: The study evaluated 200 elderly persons, among whom women predominated (56.5%). The average age was 65 years ±10. The NSAIDs accounted for 38.7% of prescription drugs used, and included dipyrone (26.9%), nimesulide (22.8%) and ketoprofen (16.3%). A total of 8.5% of such drugs were considered inappropriate medications for the elderly. A total of 104 potential drug interactions were identified, of which 24% were considered highly clinically significant. The NSAIDs with the greatest risk of interactions were ketoprofen 46.2%, ketorolac 14.4%, nimesulide 12.5% and diclofenac 9.6%. In post-sales monitoring 30.5% of the elderly persons reported undesirable symptoms after the use of NSAIDs, with stomach discomfort the most prevalent (17%). Conclusion: The present study confirmed the importance of monitoring the use of NSAIDs among the elderly due to the increased risk of drug interactions and adverse reactions associated with age, concomitant diseases, multi- prescriptions and polypharmacy. The choice of appropriate drugs for the elderly, the reconciliation of all the medications taken by the patient, and effective pharmaceutical care are measures that can contribute to the rational and safe use of NSAIDs.Maschio de Lima, Tiago Aparecido; da Cruz Furini, Adriana Antônia; Calille Atique, Tábata Salum; Di Done, Patricia; Dantas Machado, Ricardo Luiz; Fernandes de Godoy, Moacir Análise de potenciais interações medicamentosas e reações adversas a antiinflamatórios não esteroides em idosos Revista Brasileira de Geriatria e Gerontologia, vol. 19, núm. 3, julio-septiembre, 2016, pp. 533-544 Universidade do Estado do Rio de Janeiro Rio de Janeiro, Brasil

SOROPREVALÊNCIA DE ANTICORPOS ANTI-TOXOPLASMA GONDII EM AMOSTRAS DE GESTANTES NO PRÉ-NATAL

Objective: The aim of this study was to evaluate the serological profile for toxoplasmosis in pregnant women of the Northwest region of Sao Paulo. Material and Methods: This was an exploratory descriptive study with quantitative and qualitative approaches, carried out between April and August 2013. We analyzed 186 medical records of pregnant women, which were collected using a standardized questionnaire by the study team. Results: The mean age of the patients was 33 years (SD ± 4.33). The prenatal care was initiated in the first quarter by 87.63% of pregnant women and 93% were primigravidae. The laboratory technique used in the serology for toxoplasmosis was the Enzyme Linked Fluorescent Assay. Immunity to Toxoplasma gondii was identified in 25.27% of pregnant women, 73.65% had negative serology and 1.08% had positive serology for IgM antibodies. Of the seropositive women, 47 were positive only for IgG antibodies. One pregnant woman was seropositive for IgM (1.04) and IgG (700.0 IU/ml). The elevated IgG avidity of 89% indicates infection for more than three months. Conclusion: The seronegative results described in most of the medical records alert about the importance of awareness of these women to the risks of contact with the protozoan during pregnancy. These findings reinforce the need for diagnostic tests for toxoplasmosis. However, seropositive results do not guarantee full protection during pregnancy due to the variability of strains and virulence of Toxoplasma gondii. DESCRIPTORS Pregnant women. Prenatal Care. Serology. Toxoplasmosis.