DEACL - Departamento de Análises Clínicas

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3'UTR polymorphism of Thymidylate Synthase gene increased the risk of persistence of pre-neoplastic cervical lesions.
(2020) Silva, Nayara Nascimento Toledo; Santos, Ana Carolina da Silva; Nogueira, Verlândia Mendes; Carneiro, Cláudia Martins; Lima, Angélica Alves
Background: Cervical cancer is caused by high-risk Human Papillomavirus (hr-HPV) infection associated with cofactors that has been analyzed as predictors of the remission or persistence of cytological abnormalities remission or persistence. These cofactors can be either environmental, epigenetic, or genetic. Polymorphism in genes of enzymes that act on one-carbon metabolism alter their activity and also may be associated with cervical carcinogenesis because they affect DNA synthesis and repair, and gene expression. Therefore, this study aimed to analyze the risk of persistence of pre-neoplastic cervical lesions according to genetic polymorphisms involved in one-carbon metabolism. Methods: Our sample consisted of 106 women, divided into two groups – Remission (n = 60), i.e., with the presence of pre-neoplastic lesions at first meeting (T1) and normal cytology after 6 months of follow-up (T2), and Persistence (n = 46), i.e., with the presence of pre-neoplastic lesions at T1 and T2. We obtained cervical samples for cytological analysis (T1 and T2), HPV detection (T1), and evaluation of polymorphism C667T of Methylenetetrahydrofolate Reductase (MTHFR C677T), A2756G of Methionine Synthase (MS A2756G), A66G of Methionine Synthase Reductase (MTRR A66G), double or triple 28 bp tandem repeat in 5′-untranslated enhanced region of Thymidylate Synthase (TSER), and 6 bp deletion at nucleotide 1494 in TS 3′-untranslated region (TS3’UTR). To analyze all genetic polymorphisms simultaneously, we calculated the Genetic Risk Score (GRS). Results: We observed no differences between the Remission and Persistence groups regarding the GRS. Also, there were no differences in the genotypic and allelic distribution of MTHFR C677T and MS A2756G polymorphisms. However, the risk of persistence was higher among women with the heterozygote genotype - ins/del [OR (IC95%): 3.22 (1.19–8.69), p = 0.021], or the polymorphic genotype – del/del [OR (IC95%): 6.50 (1.71–24.70), p = 0.006] of TS3’UTR. Conclusions: The presence of the TS3’UTR polymorphism increased the risk of persistence of cervical abnormalities. This genetic variant could be a potential marker of cervical carcinogenesis and therefore assist the follow-up of women with persistent pre-neoplastic cervical lesions.
Accelerated Blood Clearance (ABC) phenomenon favors the accumulation of tartar emetic in pegylated liposomes in BALB/c mice liver.
(2018) Lopes, Tamara Cristina Moreira; Silva, Débora Faria; Costa, Walyson Coelho; Frezard, Frederic Jean Georges; Barichello, José Mario; Barcellos, Neila Marcia Silva; Lima, Wanderson Geraldo de; Rezende, Simone Aparecida
Tartar emetic (TE) was the first drug used to treat leishmaniasis.However, its use was discontinued due to high toxicity. Association of TE with liposomes is a strategy to reduce its side effects. Pegylated liposomes (Lpeg) present lower rates of uptake by macrophages and prolonged circulation compared to their nonpegylated counterparts. However, repeated administration of Lpeg can cause an Accelerated Blood Clearance (ABC) phenomenon, whereby recognition of liposomes by antibodies results in faster phagocytosis. Thiswork evaluated the effect of TE administration on histopathological aspects and the effect of the ABC phenomenon on targeting and toxicity in mice. Our results show that treatment with free or liposomal TE had no effect on the erythrocyte count, on liver and spleen weight, and on hepatic, splenic, and cardiac histology in mice. Severe lesions were observed on the kidneys of animals treated with a single dose of free TE. Treatment with TE in Lpeg after induction of ABC phenomenon caused a significant increase in Sb level in the liver without toxicity. Furthermore, mice treated with TE in liposomes showed normal renal histopathology. These results suggest site-specific targeting of Sb to the liver after induction of ABC phenomenon with no toxicity to other organs.
Accomplishing the genotype-specific serodiagnosis of single and dual Trypanosoma cruzi infections by flow cytometry Chagas- Flow ATE-IgG2a.
(2018) Alessio, Glaucia Diniz; Araújo, Fernanda Fortes de; Sales Júnior, Policarpo Ademar; Gomes, Matheus de Souza; Amaral, Laurence Rodrigues do; Xavier, Marcelo Antônio Pascoal; Carvalho, Andréa Teixeira de; Lana, Marta de; Martins Filho, Olindo Assis
The methods currently available for genotype-specific diagnosis of T. cruzi infection still present relevant limitations, especially to identify mixed infection. In the present investigation, we have evaluated the performance of Chagas-Flow ATE-IgG2a test for early and late differential diagnosis of single and dual genotype-specific T. cruzi infections. Serum samples from Swiss mice at early and late stages of T. cruzi infection were assayed in parallel batches for genotype-specific diagnosis of single (TcI, TcVI or TcII) and dual (TcI+TcVI, TcVI+TcII or TcII+TcI) infections. The intrinsic reactivity to TcI, TcVI and TcII target antigens, including amastigote (AI/AVI/AII), trypomastigote-(TI/TVI/TII) and epimastigote (EI/ EVI/EII), at specific reverse of serum dilutions (500 to 64,000), was employed to provide reliable decision-trees for ªearlyº vs ªlateº, ªsingle vs ªdualº and ªgenotype-specificº serology. The results demonstrated that selective set of attributes ªEII 500/EI 2,000/AII 500º were able to provide high-quality accuracy (81%) to segregate early and late stages of T. cruzi infection. The sets ªTI 2,000/AI 1,000/EII 1,000º and ªTI 8,000/AII 32,000º presented expressive scores to discriminate single from dual T. cruzi infections at early (85%) and late stages (84%), respectively. Moreover, the attributes ªTI 4,000/TVI 500/TII 1,000º, ªTI 16,000/EI 2,000/EII 2,000/AI 500/TVI 500º showed good performance for genotype-specific diagnosis at early stage of single (72%) and dual (80%) T. cruzi infections, respectively. In addition, the attributes ªTI 4,000/AII 1,000/EVI 1,000º, ªTI 64,000/AVI 500/AI 2,000/AII 1,000/EII 4,000º showed moderate performance for genotype-specific diagnosis at late stage of single (69%) and dual (76%) T. cruzi infections, respectively. The sets of decision-trees were assembled to construct a sequential algorithm with expressive accuracy (81%) for serological diagnosis of T. cruzi infection. These findings engender new perspectives for the application of Chagas-Flow ATE-IgG2a method for genotype-specific diagnosis in humans, with relevant contributions for epidemiological surveys as well as clinical and post-therapeutic monitoring of Chagas disease.
Activation ofGPR40 induces hypothalamic neurogenesis through p38‐ and BDNF‐dependent mechanisms.
(2020) Engel, Daiane Fátima; Bobbo, Vanessa Cristina Dias; Solon, Carina Silva; Nogueira, Guilherme Augusto Silva; Assis, Alexandre Moura; Mendes, Natália Ferreira; Zanesco, Ariane Maria; Papangelis, Athanasios; Ulven, Trond; Velloso, Licio Augusto
Hypothalamic adult neurogenesis provides the basis for renewal of neurons involved in the regulation of whole-body energy status. In addition to hormones, cytokines and growth factors, components of the diet, particularly fatty acids, have been shown to stimulate hypothalamic neurogenesis; however, the mechanisms behind this action are unknown. Here, we hypothesized that GPR40 (FFAR1), the receptor for medium and long chain unsaturated fatty acids, could mediate at least part of the neurogenic activity in the hypothalamus. We show that a GPR40 ligand increased hypothalamic cell proliferation and survival in adult mice. In postnatal generated neurospheres, acting in synergy with brain-derived neurotrophic factor (BDNF) and interleukin 6, GPR40 activation increased the expression of doublecortin during the early diferentiation phase and of the mature neuronal marker, microtubule-associated protein 2 (MAP2), during the late diferentiation phase. In Neuro-2a proliferative cell-line GPR40 activation increased BDNF expression and p38 activation. The chemical inhibition of p38 abolished GPR40 efect in inducing neurogenesis markers in neurospheres, whereas BDNF immunoneutralization inhibited GPR40-induced cell proliferation in the hypothalamus of adult mice. Thus, GPR40 acts through p38 and BDNF to induce hypothalamic neurogenesis. This study provides mechanistic advance in the understating of how a fatty acid receptor regulates adult hypothalamic neurogenesis.
Activity of the sesquiterpene lactone goyazensolide against Trypanosoma cruzi in vitro and in vivo.
(2020) Milagre, Matheus Marques; Branquinho, Renata Tupinambá; Gonçalves, Maíra Fonseca; Assis, Gabriela Maíra Pereira de; Oliveira, Maykon Tavares de; Reis, Levi Eduardo Soares; Guimarães, Dênia Antunes Saúde; Lana, Marta de
Background: The current drugs for Chagas disease treatment present several limitations Methods: The sesquiterpene lactone goyazensolide (GZL) was evaluated regarding to cytotoxicity and trypanocidal activity against amastigotes, selectivity index (SI) in vitro, acute toxicity and anti-Trypanosoma cruzi activity in vivo. Results: The in vitro cytotoxicity in H9c2 cells was observed at doses >250 ng mL−1 of GZL and the SI were of 52.82 and 4.85 (24 h) and of 915.00 and 41.00 (48 h) for GZL and BZ, respectively. Nephrotoxicity and hepatotoxicity were not verified. Treatment with GZL of mice infected with CL strain led to a significant decrease of parasitaemia and total survival at doses of 1 and 3 mg kg−1 day−1 by oral and IV, respectively. This last group cured 12.5% of the animals (negativation of HC, PCR, qPCR and ELISA). Animals infected with Y strain showed significant decrease of parasitaemia and higher negativation in all parasitological tests in comparison to BZ and control groups, but were ELISA reactive, as well as the BZ group, but mice treated with 5.0 mg kg−1 day−1 by oral were negative in parasitological tests and survived. Conclusion: GZL was more active against T. cruzi than benznidazole in vitro and presented important therapeutic activity in vivo in both T. cruzi strains.
Additive effects of resveratrol and doxorubicin on bladder cancer cells.
(2022) Soares, Luciana Bicalho Moreira; Lima, Ana Paula Braga; Melo, André Sacramento; Almeida, Tamires Cunha; Teixeira, Luiz Fernando de Medeiros; Silva, Glenda Nicioli da
The treatment of bladder cancer remains a challenge in clinical practice. Different chemotherapeutic protocols can be used; however, it is common to observe tumor recurrence and secondary effects that result in toxicity. Doxorubicin (DOX), one of the most effective anticancer agents used to treat bladder cancer, can cause chronic cardiotoxicity, limiting its use in clinical practice. Resveratrol (RES), a natural product with potential antitumor activity against bladder cancer, is associated with rapid metabolism and low bioavailability and needs to be combined with chemotherapeutic drugs to improve its use. Our study aimed to assess the therapeutic effect of a low concentration of DOX (2µM) in combination with RES (150, 200 and 250µM) on two bladder cancer cell lines. We investigated the mechanism of interaction between the drugs by performing cytotoxicity, clonogenic, oxidative stress, cell migration, cell morphology and nuclear division index (NDI) assays. Cytotoxicity evaluation revealed an additive interaction between RES and DOX for both cell lines. Additionally, the results of cell colony formation, oxidative stress, cell migration, cell morphology and NDI assays showed that a combination of DOX and RES was more effective than RES or DOX alone. In conclusion, a low concentration of DOX combined with RES could potentiate the antitumor effects of the drugs on bladder cancer cells, thus overcoming the secondary effects caused by DOX and the low bioavailability of resveratrol.
Advances in Chagas disease chemotherapy.
(2006) Guedes, Paulo Marcos da Matta; Fietto, Juliana Lopes Rangel; Lana, Marta de; Bahia, Maria Terezinha
Chagas disease is endemic from Mexico to Argentina, where it is estimated that 16 to 18 million people are infected with its causative agent, Trypanosoma cruzi, and 100 million remain at risk of infection, emphasizing the necessity to sustain and extend control measures and strategies to combat this disease. Specific chemotherapy with benznidazole or nifurtimox has been recommended for treatment of recent and congenital infection. However, clinical trials with nifurtimox and benznidazole have shown that these compounds have very low activity in preventing the development of chronic Chagas disease. Moreover, the drugs induce a number of toxic side effects. The discovery of new active, non-toxic compounds would probably expand treatment, including those patients in which clinical manifestations are absent or can only be disclosed by more elaborate medical procedures. Recent developments in the study of basic biochemical aspects of T. cruzi have allowed for the identification of new targets for chemotherapy. Like many fungi, T. cruzi has a strict requirement for specific endogenous sterol synthesis for cell viability and growth and is extremely susceptible to sterol biosynthesis inhibitors (SBI). An intensive investigation of the potential trypanocidal effect of specific SBI has been performed, and it was demonstrated that some of these compounds exhibited suppressive and curative activity in murine and dog models of acute and chronic Chagas disease. Other potential targets for anti-T. cruzi chemotherapy that include the antiproliferative lysophospholipid analogs (evaluated in clinical trials as the first oral treatment for visceral leishmaniasis), cysteine protease inhibitors and compounds that interfere with purine salvage and inositol metabolism are also discussed.
Analysis of the cytokine profile in spleen cells from dogs naturally infected by Leishmania chagasi.
(2007) Lage, Ramon Silva; Oliveira, Guilherme Corrêa de; Busek, Solange Cristina Uber; Guerra, Luanda Liboreiro; Giunchetti, Rodolfo Cordeiro; Oliveira, Rodrigo Corrêa de; Reis, Alexandre Barbosa
Recent studies suggest that asymptomatic dogs infected with canine visceral leishmaniasis (CVL) develop a Th1 immunological profile whilst oligosymptomatic and symptomatic CVL-infected animals present a Th2 profile. In the present study, an RT-PCR method has been standardised and employed to evaluate the frequency and the semi-quantitative level of expression of the cytokines IL-4, IL-10, IL-12, INF- g and TNF- a in splenocytes of 30 dogs naturally infected with Leishmania chagasiand of 7 non-infected dogs (NID). An increase in the level of expression of IL-12 ( p = 0.059) was detected in all CVL-infected dogs compared with NID. In dogs exhibiting high parasitism, the frequency of expression of IL-10 was higher ( p = 0.011) than in animals presenting low parasitism or medium parasitism (MP) and in NID animals, whilst the level of expression of IL-10 was higher (p = 0.0094) than in animals exhibiting MP and in the NID group. Positive correlations between the levels of expression of IL-10 with respect to the progression of the disease (IL-10: r = 0.3510; p = 0.0337) and the levels of expression of IL-10 and INF- g increase in parasitism (IL-10: r = 0.3428; p = 0.0438 and INF- g: r = 0.4690; p = 0.0045) were observed. Such data suggest that CVL is marked by a balanced production of Th1 and Th2 cytokines, with a predominant accumulation of IL-10 as a consequence of an increase in parasitic load and progression of the disease, and INF- g was related with the increase in parasitic load.
Analysis using canine peripheral blood for establishing in vitro conditions for monocyte differentiation into macrophages for Leishmania chagasi infection and T-cell subset purification.
(2013) Viana, Kelvinson Fernandes; Soares, Rodrigo Dian de Oliveira Aguiar; Roatt, Bruno Mendes; Resende, Lucilene Aparecida; Lemos, Denise da Silveira; Oliveira, Rodrigo Corrêa de; Martins Filho, Olindo Assis; Moura, Sandra Aparecida Lima de; Zanini, Marcos Santos; Araújo, Márcio Sobreira Silva; Reis, Alexandre Barbosa; Giunchetti, Rodolfo Cordeiro
Canine visceral leishmaniasis (CVL) is a parasitic disease endemic in many countries, anddogs present as the major natural reservoir of the parasite, Leishmania chagasi (syn. L.infantum). Biomarkers in the canine immune system is an important technique in thecourse of developing vaccines and treatment strategies against CVL. New methodologiesfor studying the immune response of dogs during Leishmania infection and after receivingvaccines and treatments against CVL would be useful. In this context, we used peripheralblood mononuclear cells (PBMCs) from healthy dogs to evaluate procedures related to (i)establishment of in vitro conditions of monocytes differentiated into macrophages infectedwith L. chagasi and (ii) purification procedures of T-cell subsets (CD4+and CD8+) usingmicrobeads. Our data demonstrated that after 5 days of differentiation, macrophages wereable to induce significant phagocytic and microbicidal activity after L. chagasi infectionand also showed increased frequency of parasitism and a higher parasite load. Although N-acetyl- _-d-glucosaminidase (NAG) levels presented similar levels of macrophage cultureand L. chagasi infection, a progressive decrease in myeloperoxidase (MPO) levels was ahallmark over 5 days of culture. High purity levels (>90%) of CD4 and CD8 T cells wereobtained on a magnetic separation column. We concluded that monocytes differentiatedinto macrophages at 5 days and displayed an intermediate frequency of parasitism andparasite load 72 h after L. chagasi infection. Furthermore, the purification system usingcanine T-lymphocyte subsets obtained after 5 days of monocyte differentiation provedefficient for CD4 or CD8 T-cell purification (≥90%). The in vitro analysis using L. chagasi-infected macrophages and purified T cells presented a prospective methodology that couldbe incorporated in CVL vaccine and treatment studies that aim to analyze the microbicidalpotential induced by specific CD4+and/or CD8+T cells.
Anti-serum validation for use in immunohistochemistry for Trypanosoma cruzi detection.
(2018) Azevedo, Paulo Hernane Rabelo; Xavier, Marcelo Antônio Pascoal; Silva, Glenda Nicioli da; Costa, Priscilla Almeida da; Carneiro, Cláudia Martins; Brasileiro Filho, Geraldo
Introduction: The detection of Trypanosoma cruzi in tissue samples is important in many situations, such as testing of the reactivation of the infection. The detection of T. cruzi nests in endomyocardial biopsies (EMB) may be useful to evaluate graft rejection. Given their scarcity, such nests are not routinely identified. To increase the diagnosis sensitivity, immunohistochemistry (IHC) may serve as a promising strategy. Here, we validate an antiserum for the detection of T. cruzi infection by IHC. Methods: We used 1) positive controls (PCs) – 13 EMB, 12 skin biopsies, and 1 heart with T. cruzi nests as sections stained with hematoxylin and eosin (HE); 2) negative controls – a) 10 explant hearts and 10 EMB with no amastigote nests or clinical/laboratory signs of chagasic infection; and b) eight samples with leishmaniasis, toxoplasmosis, or histoplasmosis; and 3) Cases – 31 EMB of chagasic patients with no parasite nests in HE sections but detected positive for T. cruzi DNA by polymerase chain reaction. As a primary antibody, a hyperimmune serum from T. cruzi-infected rabbits was used. Results: IHC results were positive for 21 of 26 PCs (80.8%) and one case of cutaneous leishmaniasis. In 4 of 31 cases, IHC revealed nests (12.9%), which were undetected by conventional histological examination. Conclusions: This study shows that IHC with the tested antiserum increases the sensitivity of the diagnosis and may be recommended for routine use in EMB analyses of cardiac transplant patients with Chagas disease.
Antigenic extracts of Leishmania braziliensis and Leishmania amazonensis associated with saponin partially protects BALB/c mice against Leishmania chagasi infection by suppressing IL-10 and IL-4 production.
(2010) Grenfell, Rafaella Fortini Queiroz; Silva, Eduardo de Almeida Marques da; Testasicca, Miriam Conceição de Souza; Coelho, Eduardo Antônio Ferraz; Fernandes, Ana Paula; Afonso, Luís Carlos Crocco; Rezende, Simone Aparecida
This study evaluated two vaccine candidates for their effectiveness in protecting BALB/c mice against Leishma¬nia chagasi infection. These immunogenic preparations were composed of Leishmania amazonensis or Leishmania braziliensis antigenic extracts in association with saponin adjuvant. Mice were given three subcutaneous doses of one of these vaccine candidates weekly for three weeks and four weeks later challenged with promastigotes of L. chagasi by intravenous injection. We observed that both vaccine candidates induced a significant reduction in the parasite load of the liver, while the L. amazonensis antigenic extract also stimulated a reduction in spleen parasite load. This protection was associated with a suppression of both interleukin (IL)-10 and IL-4 cytokines by spleen cells in response to L. chagasi antigen. No change was detected in the production of IFN-γ. Our data show that these im-munogenic preparations reduce the type 2 immune response leading to the control of parasite replication.
Antigenicity of a whole parasite vaccine as promising candidate against canine leishmaniasis.
(2008) Giunchetti, Rodolfo Cordeiro; Reis, Alexandre Barbosa; Lemos, Denise da Silveira; Martins Filho, Olindo Assis; Oliveira, Rodrigo Corrêa de; Bethony, Jeffrey Michael; Vale, André Macedo; Quetz, Josiane da Silva; Bueno, Lilian Lacerda; Silva, João Carlos França da; Nascimento, Evaldo do; Mayrink, Wilson; Fujiwara, Ricardo Toshio
Human visceral leishmaniasis, one of the most important zoonoses, is caused by the protozoaLeishmania chagasi(syn. L. infantum ) and is present as a fatal disease common in South America and Europe where dogs and wild canids are the main reservoirs. A vaccine against visceral leishmaniasis would be an important tool in the control of this disease in dogs. Although the current strategies for vac-cination against leishmaniasis are based on the use of recombinant antigens, killed vaccines are still attractive in terms of stability of their biochemical composition and antigenicity, cost, and safety. Here we evaluate the immunogenicity of a whole parasite vaccine as a prom-ising candidate against canine leishmaniasis, demonstrated by cellular reactivity, changes in the cellular profile of the peripheral blood and by the differential production of immunoglobulins. Our results showed that immunization elicited mainly a strong cellular reactivity and increase in T-lymphocytes, particularly the subpopulation CD8 + that would be related to the control of tissue parasitism. In addi-tion, a higher production of anti- Leishmania total IgG, characterized by mixed isotypes profile (IgG1 and IgG2), was demonstrated.
Antitumor effect of Cymbopogon densiflorus (Linneu) essential oil in bladder cancer cells.
(2020) Pereira, Gizele Lucia da Costa; Almeida, Tamires Cunha; Seibert, Janaína Brandão; Amparo, Tatiane Roquete; Soares, Rodrigo Dian de Oliveira Aguiar; Rodrigues, Ivanildes Vasconcelos; Souza, Gustavo Henrique Bianco de; Santos, Orlando David Henrique dos; Silva, Glenda Nicioli da
The aim of this study was to analyse the antitumor effect of the Cymbopogon densiflorus essential oil in silico and in vitro on bladder cancer cells RT4 and T24, with different TP53 status. The oil was extracted by hydrodistillation and the gas chromatography coupled to the mass spectrometry was used for characterisation. In silico analysis was carried out by Pass online software. Cytotoxicity, cell proliferation, cell cycle progression, apoptosis and wound healing assays were performed. Five major compounds were identified. In silico analysis showed that major compounds present high potential for antitumor activities. The treatment with C. densiflorus essential oil reduced cell viability of bladder cancer cells. Only in wild-type cells, the increase of apoptosis rates and the decrease of cell migration were observed. In conclusion, the C. densiflorus essential oil presents antitumor effects on TP53 wild-type and mutated bladder cancer cells, however, the mechanism of action is TP53 status-dependent.
Antitumoral activity of micellar solutions containing allyl isothiocyanate : an in vitro study.
(2021) Almeida, Tamires Cunha; Oliveira, Daiane Teixeira de; Sávio, André Luiz Ventura; Perasoli, Fernanda Barçante; Silva, Glenda Nicioli da; Barichello, José Mario
Introduction: Several natural products exhibit promising antineoplastic activity against bladder cancer cells, including allyl isothiocyanate (AITC). However, the AITC irritates the mucous membranes and induces eczematous or vesicular skin reactions. Thus, pharmaceutical formulations are necessary to overcome these problems. The aim was to develop micellar solutions containing AITC and investigate their antitumoral activity in bladder carcinoma cell lines. Method: The micellar solutions were prepared by cold dispersion method. Subsequently, we evaluated cytotoxicity, cell proliferation, cell cycle kinetics and long-term effects of micelles in bladder cancer cells. Results: Cytotoxicity and cell proliferation assays showed there was an increase in AITC activity when it was encapsulated in micelles. We also observed cell cycle arrest in the S phase after treatment with AITC-micelles. Furthermore, the formulation was able to maintain the long-term effects of free AITC. Conclusions: The micellar solutions developed can become an interesting approach for administration of AITC in the treatment of bladder cancer.
Apolipoprotein e polymorphism in Brazilian dyslipidemic individuals : Ouro Preto study.
(2007) Lana, Angelo Mendes; Pena, Geórgia das Graças; Freitas, Silvia Nascimento de; Lima, Angélica Alves; Nicolato, Roney Luiz de Carvalho; Nascimento Neto, Raimundo Marques do; Coelho, George Luiz Lins Machado; Freitas, Renata Nascimento de
The influence of apolipoprotein E alleles and genotypes on plasma lipid levels was determined in 185 individuals of mixed ethnicity living in Ouro Preto, Brazil. DNA was obtained from blood samples and the genotypes were determined by an RFLP-PCR procedure. The *3 allele was the most frequent (72%), followed by *4 (20%) and *2 (8%); *4 frequency was higher and *2 frequency was lower in the dyslipidemic group than in the normal control group. The *2 carriers presented lower LDL and total cholesterol levels compared to the *3 and *4 carriers. All six expected genotypes were observed in the individuals genotyped: E2/2 (2.1%), E4/4 (2.7%), E2/4 (3.7%), E2/3 (8.0%), E3/3 (53.3%), E3/4 (29.9%); no difference in genotype frequencies was found between the normal and dyslipidemic groups. Compared with *2, the presence of *3 increases more than two times the risk for dyslipidemia (OR = 2.31; P = 0.025; 95% CI = 1.06-5.06) and the presence of *4 increases it three times (OR = 3.31; P = 0.006; 95% CI = 1.36-8.04). The only significant effect of genotype was an increased risk for dyslipidemia in the *4 genotype carriers (E3/4 + E4/ 4) compared with the *2 genotype carriers (E2/2 + E2/3) with OR = 3.69 (95% CI = 1.25-10.88). The present study indicates that in the Ouro Preto admixed population the presence of APOE *2 can confer a protective effect, whereas the presence of APOE *4 implies an enhanced risk for dyslipidemia.
Association of serum folate and vitamin B12 with pre-neoplastic cervical lesions.
(2020) Silva, Nayara Nascimento Toledo; Santos, Ana Carolina da Silva; Carneiro, Cláudia Martins; Lima, Angélica Alves
Background & aims: Diet and lifestyle play an important role in etiology of various tumors. Serum concentration of folate and vitamin B12may be associated with carcinogenesis since they are involved in DNA methylation and nucleotide synthesis. However, the role of these micronutrients on development of cervical cancer is still controversial. Thus, the aim of this study was to analyze the association of lower status of folate and vitamin B12 with the risk of pre-neoplastic cervical lesions. Methods: Our sample group was divided in Control group (n ¼ 120) - women with normal cytology, and Case groups (n ¼ 57) e women presenting Atypical Squamous Cells of Undetermined Significance (ASCUS, n ¼ 21), Low Grade Squamous Intraepithelial Lesion (LSIL; n ¼ 16), and High-Grade lesions (n ¼ 20). We obtained cervical samples for cytology analysis and HPV detection, and blood samples for evaluation of serum concentration of folate and vitamin B12. Results: No difference of serum folate was observed among Cases and Control groups. On the other hand, women with High-Grade lesions presented significant lower median concentration of vitamin B12 if compared to another groups. Then, we observed increased risk of High-Grade lesions among participants with low vitamin B12 levels was observed in relation to women that presented high levels of the micronutrient and from Control group [OR (95% CI): 2.09 (0.65e6.76), p ¼ 0.216], ASC-US [OR (95% CI): 3.15 (0.82e12.08), p ¼ 0.095], and LSIL [OR (95% CI): 3.10 (0.76e12.70), p ¼ 0.116]. Conclusions: Low concentration of vitamin B12 was associated with an increased risk of High-Grade cervical lesions. Besides, we did not observe any difference of serum folate among women with normal cytology and women with pre-neoplastic cervical lesions.
Autochthonous canine visceral leishmaniasis in a non-endemic area : Bom Sucesso, Minas Gerais State, Brazil.
(2008) Silva, Marcio Roberto; Marques, Marcos José; Romanha, Alvaro José; Santa Rosa, Idael Christiano de Almeida; Carneiro, Cláudia Martins; Reis, Alexandre Barbosa
O presente trabalho descreve inicialmente um cão com sintomas característicos de leishmaniose visceral. Amostra de soro desse cão foi positiva por imunofluorescência indireta (IFI) conduzida no IgG total anti- Leishmania em 1999. Além disso, tecidos desse cão foram positivos por reação em cadeia pela polimerase (PCR) conduzida em 2004, identificando DNA de Leishmania no cerebelo, fígado, rim e intestino. Esta é a primeira vez que um cão com leishmaniose visceral autóctone foi descrito no Município de Bom Sucesso, Minas Gerais, Brasil. O achado desse cão reagente à IFI levou a uma investigação epidemiológica nesse município. Essa investigação foi conduzida de março de 1999 a dezembro de 2005. Vinte e dois de um total de 734 (3%) cães examinados foram reagentes à IFI. Entre os 22 cães IFI reagentes, seis apresentaram sintomas característicos de leishmaniose visceral canina. Os resultados desta investigação epidemiológica foram enviados às autoridades locais e estaduais de saúde pública requerendo medidas preventivas e de controle para leishmaniose visceral de forma a interromper a transmissão da doença e evitar a ocorrência de casos humanos.
Avaliação da frequência de espécies de candida isoladas em secreções vaginais e do perfil de susceptibilidade a antifúngicos.
(2020) Rodrigues, Dênis Daniel; Silva, Matheus Felipe da Cruz; Bicalho, Patrícia Helena do Nascimento; Sousa, Mireille Angela Bernardes; Ricci, Natasha Delaqua; Almeida, Isabela Neves de
A candidíase é um dos grandes problemas de saúde que levam mulheres a um quadro de infecção do aparelho reprodutor. É uma infecção causada por leveduras do gênero Candida. Essa patologia pode acometer ambos os gêneros e qualquer faixa etária desde o neonato até idosos. O método de identificação da candidíase vulvovaginal envolve as etapas da coleta, cultura e identificação do microrganismo, e para estabelecer um melhor esquema de tratamento o antifungigrama deve ser realizado. Neste contexto, o objetivo deste estudo foi avaliar a prevalência das principais espécies causadoras de candidíase vulvovaginal, bem como avaliar o respectivo perfil de sensibilidade e resistência aos antifúngicos. Foram analisadas 736 culturas de secreção vaginal no período de janeiro a março de 2017 em um laboratório de grande porte da região metropolitana de Belo Horizonte. Entre o total de 249 amostras positivas, a espécie mais prevalente foi a Candida albicans. Em relação aos antifúngicos resistentes, o Fluconazol obteve maior número de resistência com 11 cepas (28%) seguidas da Caspofungina com 4 cepas (10%). Voriconazol com 3 cepas resistentes (8%) e finalmente a Anfotericina B, Flucitosina e Micafungina com 1 cepa resistente cada. Portanto conclui-se que as espécies de Candida albicans isoladas nesse estudo apresentam maior resistência ao Fluconazol, e este fato alerta para os riscos da resistência Fonseca induzida por consequência dos tratamentos empíricos, da automedicação, assim como das infecções de repetição.
Avaliação de dislipidemia e risco cardiovascular em mulheres no climatério.
(2020) Gouvea, Thiago Magalhães; Serpa, Miguel Arcangelo; Lopes, Ana Cláudia Faria; Veloso, Vanja Maria; Gaede Carrillo, Maria Ruth Gonçalves; Lima, Angélica Alves
Este trabalho teve como objetivo avaliar a frequência de dislipidemias e determinar o risco cardiovascular de mulheres no climatério, comparando as fases pré e pós-menopausa. Foram entrevistadas 80 mulheres na faixa etária de 45 a 60 anos. As dislipidemias foram analisadas pela classificação laboratorial recomendada pela V Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose, após a realização da coleta de sangue e a determinação do perfil lipídico. O risco cardiovascular (RCV) foi avaliado pelo Escore de Risco Global (ERG). Na análise do perfil lipídico, os níveis séricos médios de colesterol total e colesterol LDL aumentaram significativamente (p<0,05) da pré para a pós-menopausa. A frequência de dislipidemias foi 51,2% (n=41), estando estatisticamente associada ao status menopausal (p=0,025). Colesterol HDL baixo isolado ou associado a hipertrigliceridemia e/ou hipercolesterolemia foi o tipo de dislipidemia mais prevalente tanto na pré (40,0%, n=8), quanto na pós-menopausa (60,0%, n=12). No geral, foi observado que, pelo Escore de Risco Global, 35% das participantes apresentaram alto risco, sendo que antes da menopausa 6,5% estavam em alto risco cardiovascular, aumentando para 53,1% na pós-menopausa. No geral, colesterol total, LDL colesterol e dislipidemias em mulheres climatéricas foram associados ao status menopausal, apontando uma progressão para um perfil mais aterogênico e de maior risco de doença cardiovascular (DCV) da fase reprodutiva para a pós-menopausa.
Avaliação do desempenho dos serviços de atenção primária à saúde no controle da tuberculose em metrópole do Sudeste do Brasil.
(2021) Rabelo, Juliana Veiga Costa; Navarro, Pedro Daibert de; Carvalho, Wânia da Silva; Almeida, Isabela Neves de; Oliveira, Camila Stefânie Fonseca; Haddad, João Paulo Amaral; Miranda, Silvana Spíndola de
A Organização Mundial da Saúde destaca a importância da organização e do desempenho dos serviços de saúde nas ações de controle da tuberculose. O objetivo deste estudo foi avaliar o desempenho dos serviços de atenção primaria à saúde em Belo Horizonte, Minas Gerais, Brasil, em relação às ações de controle da tuberculose nos eixos Estrutura e Processo, antes e após a utilização do instrumento validado denominado Estratificação por Grau de Risco Clínico e de Abandono do Tratamento da Tuberculose (ERTB). Estudo descritivo e prospectivo, no qual foram realizadas duas entrevistas (455 profissionais), tendo a segunda ocorrido após a ERTB. A classificação do desempenho seguiu os valores: ≤ 49,9%, críticos; entre 50% e 79,9%, insatisfatórios; e, ≥ 80%, satisfatórios. Na avaliação comparativa, foi utilizado o teste estatístico de McNemar, com p < 0,05. Após a estratificação de risco, a maior parte das variáveis de cada eixo melhorou significativamente. Nós concluímos que, por meio de um questionário padronizado, foi possível identificar o desempenho satisfatório dos serviços de atenção primária à saúde em Belo Horizonte em relação às ações de controle da tuberculose, na maioria das variáveis avaliadas nos eixos Estrutura e Processo.

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