Cytotoxicity and genotoxicity of low doses of mercury chloride and methylmercury chloride on human lymphocytes in vitro

Mercury is a xenobiotic metal that is a highly deleterious environmental pollutant. The biotransformation of mercury chloride (HgCl2) into methylmercury chloride (CH3HgCl) in aquatic environments is well-known and humans are exposed by consumption of contaminated fish, shellfish and algae. The objective of the present study was to determine the changes induced in vitro by two mercury compounds (HgCl2 and CH3HgCl) in cultured human lymphocytes. Short-term human leukocyte cultures from 10 healthy donors (5 females and 5 males) were set-up by adding drops of whole blood in complete medium. Cultures were separately and simultaneously treated with low doses (0.1 to 1000 µg/l) of HgCl2 and CH3HgCl and incubated at 37ºC for 48 h. Genotoxicity was assessed by chromosome aberrations and polyploid cells. Mitotic index was used as a measure of cytotoxicity. A significant increase (P < 0.05) in the relative frequency of chromosome aberrations was observed for all concentrations of CH3HgCl when compared to control, whether alone or in an evident sinergistic combination with HgCl2. The frequency of polyploid cells was also significantly increased (P < 0.05) when compared to control after exposure to all concentrations of CH3HgCl alone or in combination with HgCl2. CH3HgCl significantly decreased (P < 0.05) the mitotic index at 100 and 1000 µg/l alone, and at 1, 10, 100, and 1000 µg/l when combined with HgCl2, showing a synergistic cytotoxic effect. Our data showed that low concentrations of CH3HgCl might be cytotoxic/genotoxic. Such effects may indicate early cellular changes with possible biological consequences and should be considered in the preliminary evaluation of the risks of populations exposed in vivo to low doses of mercury.Faculdade de Itaituba Departamento de Pós-GraduaçãoUniversidade Federal do Pará Centro de Ciências Biológicas Departamento de BiologiaUniversidade Federal do Pará Centro de Ciências Biológicas Departamento de PatologiaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de GenéticaFundação Universidade Federal de Rondônia Departamento de Medicina Laboratório de Biogeoquímica AmbientalUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MorfologiaUNIFESP, EPM, Depto. de MorfologiaSciEL

Expression pattern of Cdkn2b and its regulators in canine mammary tumors

Federal University of Pará. Biological Science Institute. Molecular Biology Laboratory. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Cultura de Tecidos e Citogenética. Ananindeua, PA, Brasil.Federal University of Pará. Biological Science Institute. Molecular Biology Laboratory. Belém, PA, Brazil.Federal University of Pará. Oncology Research Center. Belem, PA, Brazil.Federal Rural University of Amazonia. Health and Animal Production Institute. Animal Pathology Laboratory. Belém, PA, Brazil.Federal Rural University of Amazonia. Health and Animal Production Institute. Animal Pathology Laboratory. Belém, PA, Brazil.Ophir Loyola Hospital. Molecular Biology Laboratory. Belém, PA, Brazil / Federal University of Pará. Molecular Biology and Human Cytogenetics Laboratory. Belém, PA, Brazil.Federal University of Pará. Biological Science Institute. Molecular Biology Laboratory. Belém, PA, Brazil.Federal University of Pará. Biological Science Institute. Molecular Biology Laboratory. Belém, PA, Brazil.Background/Aim: In female dogs, mammary cancer is the most frequent cancer type, accounting for 50% of all tumors affecting these animals. Amongst the commonly altered genes in cancer is the cell-cycle regulator cyclin-dependent kinase inhibitor 2B (Cdkn2b), whose expression is negatively regulated by protein products of BMI1 proto-oncogene (Bmi1), MYC proto-oncogene (Myc) and T-box gene transcription factor 2 (Tbx2) genes. Considering this, the aim of this study was to evaluate the expression pattern of the Cdkn2b gene and these regulators in canine mammary tumors of dogs from Northern Brazil (Belém, Pará). Material and Methods: Gene expression in samples from 33 animals was assessed by real-time polymerase chain reaction. To check the influence of methylation on gene expression, bisulfite sequencing polymerase chain reaction was also performed. Results: All studied genes, except Cdkn2b, were found at increased expression levels in tumor tissue when compared with control samples. No correlation between expression and methylation data was observed. Conclusion: Our results suggest these markers may have a diagnostic value in the veterinary clinic

Research for Cytomegalovirus Mutations Associated With Resistance to Antivirals in Kidney Transplant Receptors

Cytomegalovirus (CMV) mutations associated with antiviral resistance have become a major problem related to high mortality in kidney transplant patients. The aim of the study was to investigate mutations in the CMV genes UL97 and UL54 associated with antiviral resistance. A retrospective observational cohort study was carried out at Hospital Ophir Loyola (HOL), a reference in Kidney Transplantation. A total of 81 patients who underwent kidney transplantation were followed up between 2016 and 2018 were monitored for CMV viral load by performing qPCR. Sanger sequencing was performed on 66 patients. All CMV-positive kidney transplant recipients were included. Mutations were observed in 15 samples (22.72%) from patients. Most cases involved UL97 mutations. Mutation in UL54 without mutation in UL97 was detected in only 2 cases. Resistance mutations in UL97 were identified, such as M460V, L595S, H520Q, two co-mutations D465R + Del524 and A594P + D413A and a 3 codon deletion (del598-601). The search for mutations in the CMV genes identified mutations that confer resistance to conventional antivirals, such as ganciclovir and cidofovir, used in the treatment of these patients. Confirmation of the association with increased CMV viral load in transplanted patients, due to mutation in resistance genes, requires phenotypic analysis for confirmation purposes. These were the first findings in patients in northern Brazil that we know of

Hepatitis C and Human Pegivirus Coinfection in Patients with Chronic Hepatitis C from the Brazilian Amazon Region: Prevalence, Genotypes and Clinical Data

Coinfection of HPgV-1 with hepatitis C virus (HCV) is common due to shared modes of transmission, with a prevalence of HPgV-1 viremia of approximately 20% among individuals with chronic HCV infection. The aim of the present study was to estimate the prevalence of HPgV-1 RNA and circulating genotypes in patients with hepatitis C from a health service located in the city of Belém, in the state of Pará, Northern Brazil. A total of 147 samples were included in the study from February to December 2019. Among the participants, 72.1% (106/147) were monoinfected with HCV, with detectable HCV viral RNA, and 27.9% (41/147) were coinfected with HCV/HPgV-1. The most frequently found genotypes were HPgV-1 genotypes 1 and 2 (36.6% and 63.4%), respectively. While for HCV there was a predominance of genotypes 1 and 3 (58.5% and 41.5%). No significant differences were found when comparing any risk, sociodemographic, or clinical factors between groups. Also, there was no statistically significant difference when relating the viral genotypes of both agents. This study indicated that the prevalence of infection by HPgV-1 is high in HCV carriers in Belém, Pará, and probably does not change the clinical course of HCV infection, however, further studies are still needed

Association of Androgenic Regulation and MicroRNAs in Acinar Adenocarcinoma of Prostate

Background: Prostate cancer represents 3.8% of cancer deaths worldwide. For most prostate cancer cells to grow, androgens need to bind to a cellular protein called the androgen receptor (AR). This study aims to demonstrate the expression of five microRNAs (miRs) and its influence on the AR formation in patients from the northern region of Brazil. Material and Methods: Eighty-four tissue samples were investigated, including nodular prostatic hyperplasia (NPH) and acinar prostatic adenocarcinoma (CaP). Five miRs (27a-3p, 124, 130a, 488-3p, and 506) were quantified using the TaqMan® Real Time PCR method and AR was measured using Western blotting. Results: Levels of miRs 124, 130a, 488-3p, and 506 were higher in NPH samples. Conversely, in the CaP cases, higher levels of miR 27a-3p and AR were observed. Conclusion: In the future, these microRNAs may be tested as markers of CaP at the serum level. The relative expression of AR was 20% higher in patients with prostate cancer, which suggests its potential as a biomarker for prostate malignancy

Number of miRNAs identified in the platelet concentrate (PC) according to miRBase version 20 on different days of storage.

<p>*days</p><p>Number of miRNAs identified in the platelet concentrate (PC) according to miRBase version 20 on different days of storage.</p

Association of Androgenic Regulation and MicroRNAs in Acinar Adenocarcinoma of Prostate

Background: Prostate cancer represents 3.8% of cancer deaths worldwide. For most prostate cancer cells to grow, androgens need to bind to a cellular protein called the androgen receptor (AR). This study aims to demonstrate the expression of five microRNAs (miRs) and its influence on the AR formation in patients from the northern region of Brazil. Material and Methods: Eighty-four tissue samples were investigated, including nodular prostatic hyperplasia (NPH) and acinar prostatic adenocarcinoma (CaP). Five miRs (27a-3p, 124, 130a, 488-3p, and 506) were quantified using the TaqMan&reg; Real Time PCR method and AR was measured using Western blotting. Results: Levels of miRs 124, 130a, 488-3p, and 506 were higher in NPH samples. Conversely, in the CaP cases, higher levels of miR 27a-3p and AR were observed. Conclusion: In the future, these microRNAs may be tested as markers of CaP at the serum level. The relative expression of AR was 20% higher in patients with prostate cancer, which suggests its potential as a biomarker for prostate malignancy

Organic effects of associating paclitaxel with a lipid-based nanoparticle system on a nonhuman primate, Cebus apella

Federal University of Pará. Institute of Biological Sciences. Human Cytogenetics Laboratory. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Human Cytogenetics Laboratory. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Human Cytogenetics Laboratory. Belém, PA, Brazil.University of São Paulo. Heart Institute. Medical School Hospital. São Paulo, SP, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Sciences. Human Cytogenetics Laboratory. Belém, PA, Brazil.Federal University of Ceará. Health Sciences Center. Department of Clinical Dentistry. Fortaleza, CE, Brazil.State University of Pará. Post Graduate Program of Amazon Parasitic Biology, Biological and Health Sciences Center. Molecular Biology Laboratory. Belém, PA, Brazil.University of Sao Paulo. Heart Institute. Medical School Hospital . São Paulo, SP, Brazil.Federal University of Pará. Institute of Biological Sciences. Human Cytogenetics Laboratory. Belém, PA, Brazil.Lipid-based nanoparticle systems have been used as vehicles for chemotherapeutic agents in experimental cancer treatments. Those systems have generally been credited with attenuating the severe toxicity of chemotherapeutic agents. This study aimed to investigate the effects of associating paclitaxel (PTX) with a lipid-based nanoparticle system on a nonhuman primate, Cebus apella, documenting the toxicity as measured by serum biochemistry, which is a detailed analysis of blood and tissue. Eighteen C. apella were studied: three animals were treated with cholesterol-rich nanoemulsion (LDE) only, without PTX, administered intravenously every 3 weeks, during six treatment cycles; six animals were treated with PTX associated with LDE at the same administration scheme, three with lower (175 mg/m2 ) and three with higher (250 mg/m2 ) PTX doses; and six animals were treated with commercial PTX, three with the lower and three with the higher doses. In the LDE-PTX group, no clinical toxicity appeared, and the weight–food consumption curve was similar to that of the controls. Two animals treated with commercial PTX presented weight loss, nausea and vomiting, diarrhea, skin flaking, 70% loss of body hair, and decreased physical activity. The use of LDE as a carrier at both lower and higher doses reduced the toxicity of the drug in this species, which is closely related to human subjects. This was observed not only by clinical, biochemical, and hematological profiles but also by the histopathological analysis. The results of this study support the assumption that lipid-based nanoparticle systems used as drug carriers can serve as valuable tools to decrease the toxicity and increase the safety of chemotherapeutic agents

Number of microRNAs highly expressed in platelet concentrate (PC), according to days of storage.

<p>Number of microRNAs highly expressed in platelet concentrate (PC), according to days of storage.</p

Association between the rs820218 Variant within the <i>SAP30BP</i> Gene and Rotator Cuff Rupture in an Amazonian Population

Background: Rotator cuff disease is one of the leading causes of musculoskeletal pain and disability, and its etiology is most likely multifactorial but remains incompletely understood. Therefore, the objective of this research was to investigate the relationship of the single-nucleotide rs820218 polymorphism of the SAP30-binding protein (SAP30BP) gene with rotator cuff tears in the Amazonian population. Methods: The case group consisted of patients who were operated on due to rotator cuff tears in a hospital in the Amazon region between 2010 and 2021, and the control group was composed of individuals who were selected after negative physical examinations for rotator cuff tears. Genomic DNA was obtained from saliva samples. For the genotyping and allelic discrimination of the selected single nucleotide polymorphism (rs820218) in the SAP30BP gene, real-time PCR was performed. Results: The frequency of the A allele in the control group was four times as high as that in the case group (AA homozygotes); an association of the genetic variant rs820218 of the SAP30BP gene with rotator cuff tears was not established (p = 0.28 and 0.20), as the A allelic frequency is ordinarily low in the general population. Conclusions: The presence of the A allele indicates protection against rotator cuff tears