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1.
Biomedicines ; 11(9)2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37760978

RESUMEN

Hyperuricemia, the metabolic alteration that leads to gout or gouty arthritis, is increasing worldwide. Glycoconjugated triazole-phthalimides show potent anti-inflammatory activity. The aim of this study was to evaluate the anti-hyperuricemia effect of glycoconjugated triazole-phthalimides. To develop hyperuricemia, groups of mice received orally potassium oxonate (250 mg/kg) for 7 days, and F2, F3 and F4 glycoconjugated triazole-phthalimides (20 mg/kg), allopurinol (300 mg/kg), and 1% carboxymethylcellulose; indomethacin (2 and 4 mg/kg) was the positive control for anti-arthritic effect. Genotoxic and mutagenic effects were evaluated by the comet and micronucleus assays, respectively. The hemolytic action of the compounds was evaluated. Phthalimides F2, F3 and F4 significantly reduced the levels of serum uric acid, creatinine and urea in hyperuricemic animals. In addition, the compounds were efficient in reducing protein denaturation in a dose-dependent manner. In an interesting way, the histopathological analysis of kidneys from groups treated with F2, F3 and F4 showed a glomerular architecture, with the Bowman's capsule and renal tubules having a normal appearance and without inflammatory changes. Also, F2 and F4 showed a small increase in micronuclei, indicating a low mutagenic effect, whilst by comet assay only, we could infer that F4 affected the frequency and damage index, thus indicating a very small genotoxic action. Similarly, the phthalimides showed a low degree of erythrocyte hemolysis (<3%). Our data demonstrate that the new glycoconjugate triazole-phthalimides have potential to treat hyperuricemia and its secondary complications, such as gouty arthritis, with a low to non-significant rate of erythrocytes hemolysis, genotoxicity and mutagenicity making these molecules strong candidates as pharmaceutical agents for treatment requiring uric-acid-lowering therapy.

2.
J. pediatr. (Rio J.) ; 99(1): 59-64, Jan.-Feb. 2023. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1422026

RESUMEN

Abstract Objective: The aim of our study was to evaluate the expression of MMP-2 and MMP-9 as a prognostic factor in patients diagnosed with Hodgkin Lymphoma (HL). Methods: In the present study, 45 paraffin biopsies from patients up to 19 years old diagnosed with HL were used in two referral hospitals in the state of Pernambuco, Brazil. Risk groups were classified into favorable and unfavorable, according to Ann Arbor. The expression of matrix metalloproteinases 2 and 9 and their inhibitors was performed by immunohistochemistry (IHC). Data were analyzed using the GraphPad Prism 5 program. Results: MMP-2 intensity pattern was stronger (> 10% of the total field) in patients with stage III/ IV and B symptoms. MMP-2 showed an association with the risk group (p = 0.0388). That is, the stronger the MMP-2 marking, the greater the unfavorable risk. However, for MMP-9 there was no difference in the stronger intensity pattern in relation to stages I/II and III/IV, only in the presence of B symptoms. MMP-9 showed an association with B Symptoms (p = 0.0411). Therefore, patients with B symptoms have higher MMP-9 expression. Conclusion: Our results suggest that MMP-2 expression is associated with HL progression. While MMP-9 expression is related to the clinical worsening of these patients. However, further studies are needed to evaluate the exact role of these proteins in hematologic malignancies.

3.
Clin. biomed. res ; 41(3): 259-261, 20210000. tab, ilus
Artículo en Inglés | LILACS | ID: biblio-1348032

RESUMEN

The present work aims to report a case of Buschke-Löwenstein tumor (BLT), which is a mass of genital warts that usually affects immunosuppressed people. The reported case was diagnosed in a young patient with no known immunosuppression. Several tests were performed to confirm the diagnostic hypothesis, including immunohistochemistry, histological, molecular and imaging analysis. The results obtained were confirmatory in all analyses, except in the molecular one. Because BLT is a rare condition, there is still great literary heterogeneity regarding the ideal treatment, but some options can be considered, such as excision and radiotherapy. (AU)


Asunto(s)
Humanos , Femenino , Adolescente , Tumor de Buschke-Lowenstein/diagnóstico , Infecciones por Papillomavirus
4.
J Med Virol ; 92(12): 3799-3806, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32989777

RESUMEN

Cervical carcinoma is the fourth leading cause of death among women worldwide. Epidemiological studies claim that human papillomavirus (HPV) infection is a necessary condition for cervical cancer development. Knowledge of the geographic distribution of HPV is important in guiding the introduction of prophylactic vaccines. This study analyzed the prevalence of HPV infection in cervical samples obtained from women with abnormal cervical histopathological diagnosis in Northeast Brazil. The study included an analysis of 211 women whose diagnosis was confirmed for cervical intraepithelial neoplasia type 1 (CIN-1), cervical intraepithelial neoplasia type 2 (CIN-2), cervical intraepithelial neoplasia type 3 (CIN-3), and cancer. The identification of the HPV genotypes was based on the polymerase chain reaction-restriction fragment length polymorphism technique. A total of 42.7% of the samples showed a single HPV infection, while 57.3% showed multiple infections. The most common genotypes detected were HPV-16, HPV-18, and HPV-31. HPV-16, HPV-31, HPV-35, and HPV-18 were the most common types in CIN-1 with a single infection. HPV-16 and HPV-18 were the most often found in CIN-2 with a single infection. HPV-16, HPV-18, and HPV-31 were the most detected in CIN-3 with a single infection. HPV-16 and HPV-31 were the most frequent in cancer with a single infection. Multiple infection with HPV-16 shows a 2.7 times greater risk of CIN-3 (P = .04). Multiple infections for HPV with HPV-16 and excluding the HPV18/31 types, were associated with CIN-3 (P = .01). The results allowed the detection and genotyping of HPV types circulating in the population studied. These findings must be taken into account when devising vaccination strategies against HPV.

5.
Cytokine ; 113: 99-104, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-29935877

RESUMEN

Human papillomavirus (HPV) is responsible for high-grade cervical lesions and cervical cancer. The inflammation plays a key role in cervical cancer progression. In this context, studies propose an association between TNFα and IL10 SNPs and susceptibility to HPV infection. The present work aimed to investigate the possible association between IL10 and TNFα promoter polymorphisms and HPV infection in the cervical carcinogenesis risk in women from Brazil. A total of 654 samples was evaluated in this study. HPV detection was performed by PCR and HPV genotyping was performed by PCR and sequencing of positive MY09/11 PCR product. Genotyping of IL10 SNPs (rs1800871 and rs1800896) was performed by High Resolution Melt analysis. Genotyping of TNFα SNP (rs1800629) was performed by fluorogenic allele-specific probes. The distribution of TNF-308 (rs1800629) allelic (p = 0.03) and genotype (p = 0.03) frequencies and HPV-58 infection has showed a statistically significant difference between case and control groups for the assessed TNFα polymorphism. When it comes to TNFα (rs1800629) allelic and genotypic distribution and HPVs 18 and 31 infections, no statistically significant differences between case and control groups were observed for the studied TNFα polymorphism. The allelic and genotypic distribution of IL10-819 (rs1800871) and IL10-1082 (rs1800896) and HPV infection (HPVs 58, 18 and 31) has showed no statistically significant differences between case and control groups for the assessed IL10 polymorphisms. Furthermore, it was observed that haplotypes were associated with an increased cervical cancer risk in HPVs 16, 18 and 58-positive women. It was observed that women carrying the GTA and ATG haplotypes had 3.85 and 17.99-fold, respectively, increased cervical cancer susceptibility when infected by HPV-58. In women infected with HPV-16 and HPV-18, statistically significant results in women carrying the GTA and ATA haplotypes was observed. They had a 2.32 and 3.67-fold, respectively, increased cervical cancer susceptibility when infected by these two HPV types. The analysis of the haplotypes distribution in women infected with HPV-31 has showed no statistically significant results. Our study indicates that the association of genetic polymorphism in inflammation-related genes represents a risk to the susceptibility in the development of cervical cancer in women infected by HPVs 16, 18 and 58.


Asunto(s)
Carcinogénesis/genética , Haplotipos/genética , Interleucina-10/genética , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/genética , Factor de Necrosis Tumoral alfa/genética , Neoplasias del Cuello Uterino/genética , Adulto , Alelos , Brasil , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Humanos , Infecciones por Papillomavirus/virología , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Neoplasias del Cuello Uterino/virología
6.
J Cancer Res Clin Oncol ; 144(12): 2367-2376, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30225539

RESUMEN

PURPOSE: Evaluate the presence of human papillomavirus (HPV) in biopsies of Brazilian patients with lung cancer and also the expression of the E6 and E7 oncoproteins. HPV is widely known as an important condition for cervical cancer although evidence today shows it is associated with several other types of cancer and may also be involved in lung cancer development. However, there are some divergences regarding the presence and activity of HPV in lung carcinogenesis. METHODS: The detection of HPV was performed by PCR, followed by genotype and immunohistochemical evaluation of E6 and E7 HPV type specific, from 63 patients. RESULTS: HPV was found to be present in 33 of the 63 samples, and types 16 and 18 were detected with frequencies of 81% (27/33) and 19% (6/33), respectively. About the presence of the virus in different histological types of tumors, HPV was detected in squamous cell carcinoma (39.39%), followed by adenocarcinoma (33.33%) and small cell carcinoma (18.18%) and large cell carcinoma (9.1%). The presence of the E6 (antibody anti-HPV 16 and anti-HPV 18) and E7 (antibody anti-HPV 16 and anti-HPV 18) oncoproteins was detected by immunohistochemical stain technique in 28/33 samples and 25/33 samples, respectively. CONCLUSIONS: Our results suggest that the lung tumor patients have high prevalence of HPV and the virus is not only present but also active in tumor cells. Therefore, the HPV is probably playing a role in lung carcinogenesis.


Asunto(s)
Neoplasias Pulmonares/etiología , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismo , Papillomaviridae/clasificación , Papillomaviridae/genética , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Adulto Joven
7.
Food Chem Toxicol ; 97: 297-306, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27644596

RESUMEN

1,8-cineole (eucalyptol) is widely used as an excipient in the pharmaceutical industry and as a food flavoring agent, thus providing significant potential for human exposure to the compound. We investigated the preclinical toxicity and reproductive toxicity of 1,8-cineole (CIN). In the repeated-doses toxicity study for 50 days, CIN (100, 500 or 1000 mg/kg) did not produce any signs of toxicity or deaths, but affected body weight gain during the first week of treatment. The hematological and biochemical profiles did not show significant differences except for increase in the MCV, platelet and urea levels or reduction in MCHC, MPV and alkaline phosphatase. Histopathological analysis showed weak changes in the lungs, liver, kidneys and uterus. In the reproductive toxicity, CIN (250, 500 or 1000 mg/kg) produced a reduction in body weight in pregnant rats treated during the pre-implantation or organogenesis periods. The highest doses induced a reduction in the mass of fetuses (pre-implantation) and dead fetuses (both periods) of pregnant rats. The results indicate that the treatment by repeated-doses showed occasional alterations in rats of both sexes. However, provide evidence that possibly 1,8-cineole presents maternal and fetal toxicity. This requires more detailed investigation to better characterize the toxic effects of this compound.


Asunto(s)
Antiinfecciosos/toxicidad , Ciclohexanoles/toxicidad , Feto/efectos de los fármacos , Exposición Materna/efectos adversos , Monoterpenos/toxicidad , Reproducción/efectos de los fármacos , Pruebas de Toxicidad/métodos , Animales , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Eucaliptol , Femenino , Humanos , Masculino , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Ratas , Ratas Wistar
8.
PLoS One ; 10(8): e0134558, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26244547

RESUMEN

Recently, our research group identified and reported 1,8-cineole (CIN), a monoterpene that naturally occur in many aromatic plants, as one of the major constituent of the essential oil from leaves of Hyptis martiusii (EOHM), as well as characterized the gastroprotective action of this oil. The aim of this study was to investigate the mechanisms of action involved in the antiulcer and healing activity of CIN, in order to confirm its correlation with the gastroprotective effect of EOHM. Wistar rats were exposed to different protocols (acute ulceration, gastrointestinal motility and antisecretory activity). In addition, were determinated the involvement of nitric oxide and sulphydryl groups; the levels of gastric mucus, lipid peroxidation, sulphydryl groups and myeloperoxidase activity. The healing ability was evaluated by acetic acid-induced chronic ulcer and histological and immunohistochemical analysis (PCNA, Ki-67 and BrdU). The treatment with CIN inhibited ethanol-, ethanol/HCl- and indomethacin-induced gastric lesions. The highest doses of CIN inhibited gastric emptying, but did not affect intestinal transit. CIN (100 mg/kg) reduced the volume of basal but not stimulated acid secretion. CIN increased levels of mucus (89.3%), prevented depletion of -SH groups (62.6%) and reduced the level of lipid peroxidation (55.3%) and myeloperoxidase activity (59.4%) in the gastric mucosa. In chronic ulcer model, CIN reduced in 43.1% the gastric area lesion, promoted significant regeneration and restoration of the levels of mucus in glandular cells as confirmed by histological analysis; and promoted increase in cell proliferation as evidenced by reactivity for PCNA, Ki-67 and BrdU. This findings demonstrate the role of 1,8-cineole as an important ulcer healing agent and indicate the involvement of antioxidant and cytoprotective mechanisms in the gastroprotective effect of compound. This study also provides evidence that 1,8-cineole is related to the gastroprotective effect of the essential oil of Hyptis martiusii.


Asunto(s)
Ciclohexanoles/farmacología , Fármacos Gastrointestinales/farmacología , Motilidad Gastrointestinal/efectos de los fármacos , Monoterpenos/farmacología , Sustancias Protectoras/farmacología , Úlcera Gástrica/prevención & control , Administración Oral , Animales , Antioxidantes/metabolismo , Bromodesoxiuridina/análisis , Ciclohexanoles/administración & dosificación , Eucaliptol , Femenino , Ácido Gástrico/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Fármacos Gastrointestinales/administración & dosificación , Hyptis/química , Inmunohistoquímica , Antígeno Ki-67/análisis , Masculino , Monoterpenos/administración & dosificación , Moco/metabolismo , Antígeno Nuclear de Célula en Proliferación/análisis , Sustancias Protectoras/administración & dosificación , Ratas Wistar , Compuestos de Sulfhidrilo/metabolismo
10.
PLoS One ; 9(11): e111021, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25365304

RESUMEN

A number of recent studies have catalogued global gene expression patterns in a panel of normal, tumoral cervical tissues so that potential biomarkers can be identified. The qPCR has been one of the most widely used technologies for detecting these potential biomarkers. However, few studies have investigated a correct strategy for the normalization of data in qPCR assays for cervical tissues. The aim of this study was to validate reference genes in cervical tissues to ensure accurate quantification of mRNA and miRNA levels in cervical carcinogenesis. For this purpose, some issues for obtaining reliable qPCR data were evaluated such as the following: geNorm analysis with a set of samples which meet all of the cervical tissue conditions (Normal + CIN1 + CIN2 + CIN3 + Cancer); the use of individual Ct values versus pooled Ct values; and the use of a single (or multiple) reference genes to quantify mRNA and miRNA expression levels. Two different data sets were put on the geNorm to assess the expression stability of the candidate reference genes: the first dataset comprised the quantities of the individual Ct values; and the second dataset comprised the quantities of the pooled Ct values. Moreover, in this study, all the candidate reference genes were analyzed as a single "normalizer". The normalization strategies were assessed by measuring p16INK4a and miR-203 transcripts in qPCR assays. We found that the use of pooled Ct values, can lead to a misinterpretation of the results, which suggests that the maintenance of inter-individual variability is a key factor in ensuring the reliability of the qPCR data. In addition, it should be stressed that a proper validation of the suitability of the reference genes is required for each experimental setting, since the indiscriminate use of a reference gene can also lead to discrepant results.


Asunto(s)
Transformación Celular Neoplásica/genética , Perfilación de la Expresión Génica , MicroARNs/genética , ARN Mensajero/genética , Neoplasias del Cuello Uterino/genética , Cuello del Útero/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estabilidad del ARN , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados
11.
PLoS One ; 9(1): e84400, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24454726

RESUMEN

Hyptis martiusii Benth. is an aromatic plant found in abundance in northeastern Brazil that is used in ethnomedicine to treat gastric disorders. The aim of this study was to elucidate the mechanisms of action involved in the gastroprotection of the essential oil of Hyptis martiusii (EOHM) and to evaluate its healing capacity. Wistar rats were exposed to different protocols and subsequently were treated with 1% Tween-80 aqueous solution (negative control), pantoprazole, carbenoxolone, N-acetylcysteine (depending on the specificity of each model) or EOHM. The antisecretory activity (basal or stimulated) was determined using the pyloric ligature method. The gastroprotective action of nitric oxide and sulphydryl groups (-SH groups), as well as the quantification of adherent mucus and the levels of malondialdehyde and -SH groups in gastric mucosa, were evaluated using ethanol-induced gastric ulcer model. The healing ability was evaluated using the acetic acid-induced gastric ulcer model and histological and immunohistochemical analysis (HE, PAS and PCNA). EOHM (400 mg/kg) reduced the volume and acidity of gastric secretion stimulated by histamine and pentagastrin. The gastroprotective effect of EOHM involves the participation of endogenous sulfhydryl groups. EOHM increased mucus production (54.8%), reduced levels of MDA (72.5%) and prevented the depletion of -SH groups (73.8%) in the gastric mucosa. The treatment with EOHM reduced in 70.3% the gastric lesion area, promoting significant regeneration of the gastric mucosa, as confirmed by histological analysis and analysis of proliferating cell nuclear antigen. The results show that gastroprotective effect of EOHM is mediated by cytoprotective and antioxidant mechanisms and by their antisecretory activity, and suggest that the essential oil of Hyptis martiusii is a promising candidate for the treatment of gastric ulcers.


Asunto(s)
Lamiaceae/química , Aceites Volátiles/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Animales , Femenino , Masculino , Aceites Volátiles/farmacología , Ratas
12.
Artículo en Inglés | MEDLINE | ID: mdl-24151521

RESUMEN

Hyptis martiusii Benth. (Lamiaceae) is found in abundance in Northeastern Brazil where it is used in traditional medicine to treat gastric disorders. Since there are no studies reporting the toxicity and safety profile of this species, we investigated repeated-doses toxicity of the essential oil of Hyptis martiusii (EOHM). Swiss mice of both sexes were orally treated with EOHM (100 and 500 mg/kg) for 30 days, and biochemical, hematological, and morphological parameters were determined. No toxicity signs or deaths were recorded during the treatment with EOHM. The body weight gain was not affected, but there was an occasional variation in water and food consumption among mice of both sexes treated with both doses. The hematological and biochemical profiles did not show significant differences except for a decrease in the MCV and an increase in albumin, but these variations are within the limits described for the species. The microscopic analysis showed changes in liver, kidneys, lungs, and spleen; however, these changes do not have clinical relevance since they varied among the groups, including the control group. The results indicate that the treatment of repeated-doses with the essential oil of Hyptis martiusii showed low toxicity in mice.

13.
J Clin Pathol ; 66(9): 775-8, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23833048

RESUMEN

AIMS: The aim of this study was to report circulating cell-free DNA using ALU247 and ALU247/ALU115 biomarkers in serum of operated and non-operated patients with colorectal cancer (CRC). METHODS: To undertake this, 90 blood samples were collected, including 30 samples from healthy volunteers; 27 samples from CRC non-operated patients and 33 samples from CRC-operated patients. Circulating cell-free DNA was verified through quantitative real-time PCR (qPCR) using ALU115 and ALU247 primers. RESULTS: With regard to the ALU115-qPCR biomarker, the increased levels of circulating cell-free DNA in serum of non-operated patients were significant when compared with control (p<0.05). Moreover, levels of ALU247-qPCR biomarker were statistically significant between non-operated versus operated and non-operated versus control groups (p=0.000). With regard to the ALU247/115-qPCR biomarker, significant differences were observed between control versus non-operated patients (p=0.019), operated versus non-operated patients (p=0.005) and control versus operated patients (p=0.043). CONCLUSIONS: Thus, the ALU247 and ALU247/ALU115-qPCR biomarkers may be important in detecting and monitoring CRC patients in both early and late stages.


Asunto(s)
Adenocarcinoma/diagnóstico , Neoplasias Colorrectales/diagnóstico , ADN/sangre , Adenocarcinoma/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Neoplasias Colorrectales/sangre , Femenino , Humanos , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad
14.
Biomed Res Int ; 2013: 546354, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23865057

RESUMEN

The aim of this study was to examine the prevalence and genetic variability of the capsid L1 gene of rare HPV genotypes that were found in the cervical lesions of women from North-East Brazil. A total number of 263 patients were included in this study. HPV detection was performed using PCR followed by direct sequencing of MY09/11, as well as type-specific PCR to detect the Alpha-9 species. Epitope prediction was performed to determine whether or not the genetic variants are inserted in B-cell and T-cell epitopes. The prevalence of rare HPV types in cervical lesions was found to be 9.47%. The rare HPV genotypes that were detected were HPV-53, 54, 56, 61, 62, 66, 70, and 81. The genetic variability in the L1 gene of rare HPV types involved thirty nucleotide changes, eight of which were detected for the first time in this study. Moreover, some of these variants are embedded in B-cell or T-cell epitope regions. The results of this research suggest that rare HPV types might be involved in cervical lesions and some of these variants can be found in B-cell and T-cell epitopes. Data on the prevalence and variability of rare HPV types will assist in clarifying the role of these viruses in carcinogenesis.


Asunto(s)
Proteínas de la Cápside/genética , Variación Genética , Papillomaviridae/genética , Neoplasias del Cuello Uterino/virología , Adolescente , Adulto , Anciano , Secuencia de Aminoácidos , Aminoácidos/genética , Secuencia de Bases , Brasil/epidemiología , Proteínas de la Cápside/química , Epítopos de Linfocito B/química , Epítopos de Linfocito T/química , Femenino , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , Prevalencia , Adulto Joven , Displasia del Cuello del Útero/virología
15.
Infect Genet Evol ; 19: 32-7, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23800422

RESUMEN

Human Papillomavirus (HPV) infection plays a crucial role in the development of cervical lesions and tumors, however most lesions containing high-risk HPVs do not progress to cervical tumors. Some studies suggest that the use of oral contraceptives may increase the risk of cervical carcinogenesis, but this has not been confirmed by all the studies. Cytokines are important molecules that act in the defense of an organism against viral infections. Several genetic studies have attempted to correlate cytokine polymorphisms with human diseases, including cancer. The significance of IL10 polymorphisms for cancer is that they have both immunosuppressive and antiangiogenic properties. We aimed to investigate the role of promoter polymorphisms in the IL10 gene in women with cervical lesions associated with HPV infection, in the presence of the use of oral contraceptives. Using High Resolution Melt analysis (HRM), we analyzed an SNP -1082A/G and -819C/T in interleukin-10 promoter region in 364 Brazilian women: 171 with cervical lesions and HPV infection, and 193 with normal cytological results and HPV-negative. We observed no significant differences in genotype and allele frequencies in the two loci between patients and healthy controls. Furthermore, in the haplotype analysis of IL10, we found that CA haplotype was significantly more frequent in patients infected with HPV than in the control group (p = 0.0188). We did not find any genotype and allelic association of the IL10 gene polymorphisms between cases and controls. However, in this study, when the HPV-positive patients were stratified according to their use of contraceptives, we found a significant association between the -1082G allele (p = 0.0162) and -1082GG genotype (p = 0.0332) among HPV-infected patients who used oral contraceptives. Our findings suggest that -1082A/G gene polymorphism represents a greater susceptibility to progressive cervical lesions in HPV- infected women who use oral contraceptives.


Asunto(s)
Anticonceptivos Orales , Interleucina-10/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Neoplasias del Cuello Uterino/genética , Adulto , Femenino , Genotipo , Haplotipos , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/epidemiología , Adulto Joven
16.
Infect Genet Evol ; 16: 13-8, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23403356

RESUMEN

HPV-31 has been widely described as an important oncogenic type, showing high incidence in worldwide and especially in Northeastern Brazil. We sought to identify the presence of specific mutations in HPV-31 E6 and E7 oncogenes in women with abnormal cervical smear. We enrolled 150 gynecological patients from Sergipe State, Northeastern Brazil. HPV screening was carried out by polymerase chain reaction (MY09/11). E6 and E7 oncogenes were amplified with specific primers and sequenced. The sequences obtained were aligned with the GenBank reference sequences in order to search for genetic variants. We identified genetic variants in E6 and E7 sequences from HPV-31. Two new nucleotide changes in E6 and E7 were described for the first time in this study. A novel mutation in E6 resulted in amino acid change in a site belonging to T-cell epitope with MHC II binding activity. There was no significant difference in the distribution of HPV-31 E6 and E7 variants when compared to all selected clinical/epidemiological characteristics. HPV-31 isolates have been clustered into three main groups called lineages A, B and C. We describe new HPV-31 variants in Brazil, contributing to better understand the genomic diversity of these viruses.


Asunto(s)
Papillomavirus Humano 31/genética , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus/genética , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/virología , Adolescente , Adulto , Brasil/epidemiología , Femenino , Variación Genética , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/epidemiología , Filogenia , Neoplasias del Cuello Uterino/epidemiología
17.
São Paulo; s.n; 2008. 122 p. ilus, tab, graf.
Tesis en Portugués | LILACS, Coleciona SUS, Sec. Est. Saúde SP, SESSP-CTDPROD, Sec. Est. Saúde SP, SESSP-ACVSES, SESSP-IALPROD, Sec. Est. Saúde SP, SESSP-IALACERVO, SESSP-TESESESSP, Sec. Est. Saúde SP | ID: biblio-933369

RESUMEN

O carcinoma mamário apresenta elevados números relacionados à incidência e prevalência nas mulheres em vários países. No Brasil, é a neoplasia com um dos maiores índices de mortalidade. O tipo de carcinoma mamário mais freqüente é o ductal invasor seguido do carcinoma lobular. Embora essas neoplasias tenham características próprias, há ainda muitas questões a serem dirimidas. Sabe-se que os carcinomas lobulares apresentam alto risco de desenvolvimento bilateral e recorrência; estão relacionadas à expressão hormonal e têm desfecho lento. Sabe-se que o carcinoma lobular não tem positividade para a proteína E-caderina, cuja ausência de expressão imuno-histoquímica tem sido usada para diferenciá-la do carcinoma ductal. O padrão do conteúdo de DNA no carcinoma lobular tem sido objeto de controvérsias, com trabalhos descrevendo-o como predominantemente diplóide e outros, ao contrário, aneuplóide. O objetivo deste estudo foi analisar os padrões da DNA-ploidia em carcinomas lobulares invasivos de mama, E-caderina negativos, e correlacioná-los com fatores prognósticos de notória importância: expressão da proteína p53, Cerb-B2, receptores de estrógeno, tamanho dos tumores, comprometimento linfonodal, metástases a distância e pós-cirúrgica. Para isso foi realizado um estudo retrospectivo, com 50 casos examinados no Departamento de Anatomia Patológica do Hospital do Câncer A. C. Camargo, São Paulo-SP. Essas mulheres foram tratadas com cirurgia e as que apresentaram comprometimento axilar, receberam terapia adjuvante com quimioterapia, radioterapia e hormônioterapia. As medianas dos tempos de seguimento, com início no tratamento inicial (cirurgia) até o evento foi: grupo que foram a óbito 50 ± 27,6 meses; grupo com perda de seguimento 33 ± 56,0 meses; grupo de censura por interrupção do tempo para análise 79 ± 45,3 meses. A idade média foi de 54 anos (variando de 34 a 80 anos). A análise ...


Asunto(s)
Neoplasias de la Mama , Cadherinas/ultraestructura , Carcinoma Lobular , Carcinoma Lobular/patología , Citometría de Imagen/métodos
18.
São Paulo; s.n; 2008. 122 p. ilus, tab, graf.
Tesis en Portugués | LILACS, SESSP-CTDPROD, Sec. Est. Saúde SP, SESSP-IALPROD, Sec. Est. Saúde SP | ID: lil-507353

RESUMEN

O carcinoma mamário apresenta elevados números relacionados à incidência e prevalência nas mulheres em vários países. No Brasil, é a neoplasia com um dos maiores índices de mortalidade. O tipo de carcinoma mamário mais freqüente é o ductal invasor seguido do carcinoma lobular. Embora essas neoplasias tenham características próprias, há ainda muitas questões a serem dirimidas. Sabe-se que os carcinomas lobulares apresentam alto risco de desenvolvimento bilateral e recorrência; estão relacionadas à expressão hormonal e têm desfecho lento. Sabe-se que o carcinoma lobular não tem positividade para a proteína E-caderina, cuja ausência de expressão imuno-histoquímica tem sido usada para diferenciá-la do carcinoma ductal. O padrão do conteúdo de DNA no carcinoma lobular tem sido objeto de controvérsias, com trabalhos descrevendo-o como predominantemente diplóide e outros, ao contrário, aneuplóide. O objetivo deste estudo foi analisar os padrões da DNA-ploidia em carcinomas lobulares invasivos de mama, E-caderina negativos, e correlacioná-los com fatores prognósticos de notória importância: expressão da proteína p53, Cerb-B2, receptores de estrógeno, tamanho dos tumores, comprometimento linfonodal, metástases a distância e pós-cirúrgica. Para isso foi realizado um estudo retrospectivo, com 50 casos examinados no Departamento de Anatomia Patológica do Hospital do Câncer A. C. Camargo, São Paulo-SP. Essas mulheres foram tratadas com cirurgia e as que apresentaram comprometimento axilar, receberam terapia adjuvante com quimioterapia, radioterapia e hormônioterapia. As medianas dos tempos de seguimento, com início no tratamento inicial (cirurgia) até o evento foi: grupo que foram a óbito 50 ± 27,6 meses; grupo com perda de seguimento 33 ± 56,0 meses; grupo de censura por interrupção do tempo para análise 79 ± 45,3 meses. A idade média foi de 54 anos (variando de 34 a 80 anos). A análise do conteúdo de DNA mostrou-se predominantemente aneuplóide (63,16 % dos casos). Somente o comprometimento linfonodal mostrou-se significativo (p=0,043) em relação a análise de DNA-ploidia, os demais parâmetros não mostraram associação significativa. Concluímos que a análise do conteúdo de DNA não é um parâmetro relevante para avaliar a agressividade do carcinoma lobular.


Asunto(s)
Neoplasias de la Mama , Carcinoma Lobular , Cadherinas/ultraestructura , Carcinoma Lobular/patología , Citometría de Imagen/métodos
19.
Rev. bras. anal. clin ; 32(4): 279-83, 2000. tab, graf
Artículo en Portugués | LILACS | ID: lil-296345

RESUMEN

O climatério é marcado por mudanças somáticas e psíquicas. Costuma iniciar numa faixa etária que vai de 40 a 55 anos de idade. Este estudo analisou cinqüenta mulheres (n=50) que näo faziam uso de reposiçäo hormonal e medicaçäo para cardiopatias, residentes no interior de Pernambuco - Brasil. Foram realizadas dosagens bioquímicas no sangue com os seguintes resultados: glicose - 86,7 porcento das mulheres eram normoglicêmicas e 13,3 porcento hiperglicêmicas, com média de 102,43 mg/dl. Transaminase (TGP) com média de 16,38 unidade F.R./ml, 97,8 porcento com níveis normais. O colesterol total apresentou média igual a 222,3 mg/dl. 77,8 porcento das mulheres se apresentaram hipercolesterolêmicas. Na avaliaçäo hormonal a dosagem de estradiol e progesterona foi realizada dividindo a amostra estudada em três grupos: A, B e C. O grupo A, formado por mulheres com ciclos menstruais normais (n=31), utilizado como controle, apresentou 90,32 porcento com níveis normais de estradiol. O grupo B, composto por mulheres com ciclos irregulares (n=6) onde 100 porcento das pacientes estavam dentro da normalidade para esta fase. O grupo C, representado por mulheres menopausadas (n=13), acima de doze meses de amenorréia, 69,23 porcento apresentaram níveis dentro do esperado e 30,77 porcento acima. A média do nível de estradiol foi 58,12 pg/ml (p<0,00174). Na determinaçäo da progesterona, o grupo A obteve 100 porcento das pacientes apresentando níveis dentro da normalidade. O grupo B também 100 porcento dentro da normalidade. No grupo C, 84,62 porcento estavam dentro da normalidade para a faixa etária e 15,38 porcento com níveis acima do esperado. A média geral foi 4,11 ng/ml. Na citologia foram encontrado 68,9 porcento dos esfregaços normotróficos, 24,4 porcento hipotróficos e 6,7 porcento säo atróficos. As mulheres menopausadas apresentaram um grande percentual de normotrofismo apesar de mostrarem baixos os níveis de estradiol. Os níveis de progesterona sofreram um decréscimo significativo porém sem alterar o trofismo cérvico-vaginal, mostrando que näo existe uma correlaçäo direta. Os resultados sugerem que a reposiçäo hormonal deve ser bastante criteriosa e estudada caso a caso, levando em grande consideraçäo os níveis de estradiol e progesterona e o padräo de trofismo cérvico-vaginal


Asunto(s)
Humanos , Femenino , Adulto , Persona de Mediana Edad , Estradiol/análisis , Menopausia/sangre , Progesterona/análisis , Alanina Transaminasa/química , Glucemia/química , Colesterol/química , Frotis Vaginal/métodos , Radioinmunoensayo , Terapia de Reemplazo de Hormonas
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