Açaí (Euterpe oleracea Mart.) Seed Oil Exerts a Cytotoxic Role over Colorectal Cancer Cells: Insights of Annexin A2 Regulation and Molecular Modeling.

Açaí, Euterpe oleracea Mart., is a native plant from the Amazonian and is rich in several phytochemicals with anti-tumor activities. The aim was to analyze the effects of açaí seed oil on colorectal adenocarcinoma (ADC) cells. In vitro analyses were performed on CACO-2, HCT-116, and HT-29 cell lines. The strains were treated with açaí seed oil for 24, 48, and 72 h, and cell viability, death, and morphology were analyzed. Molecular docking was performed to evaluate the interaction between the major compounds in açaí seed oil and Annexin A2. The viability assay showed the cytotoxic effect of the oil in colorectal adenocarcinoma cells. Acai seed oil induced increased apoptosis in CACO-2 and HCT-116 cells and interfered with the cell cycle. Western blotting showed an increased expression of LC3-B, suggestive of autophagy, and Annexin A2, an apoptosis regulatory protein. Molecular docking confirmed the interaction of major fatty acids with Annexin A2, suggesting a role of açaí seed oil in modulating Annexin A2 expression in these cancer cell lines. Our results suggest the anti-tumor potential of açaí seed oil in colorectal adenocarcinoma cells and contribute to the development of an active drug from a known natural product.

Impact of HPV-16 Lineages Infection in Response to Radio-Chemotherapy in Cervical Cancer.

BACKGROUND: HPV is strongly related to cervical cancer. HPV lineages can contribute to a response to cervical cancer therapy. The aim of this research was to estimate the frequency of human papillomavirus (HPV)-16 lineages in specimens of cervical cancer, relate the pathological factors in these variants, and assess their response to treatment with radical chemoradiotherapy. METHODS: Samples of cervical cancer were collected from women who were referred to a reference cancer hospital to test the presence of human papillomavirus-type DNA. The standard protocol of this service consisted of cisplatin-based chemotherapy of 40 mg/m2, plus conventional pelvic irradiation in doses of 45-50.4 Gy and high dose-rate brachytherapy of 28-30 Gy to Point A. The response to chemotherapy was evaluated after three months in patients with the HPV-16 lineage. RESULTS: HPV DNA was detected in 104 (88.1%) of the 118 patients. HPV-16 was present in 63 patients (53%). Lineages of HPV-16 were identified in 57 patients and comprised 33 instances of (57.8%) lineage A, 2 instances of lineage B (3.5%), 2 instances of lineage C (3.5%), and 20 instances of (35.0%) lineage D. The median age of the patients was 48.4 years (range 25-85 years). Squamous cell carcinoma was detected 48 times (84.2%). Adenocarcinoma was more likely to occur in lineage D, as three of the four cases occurred in this lineage. A total of 11 patients with the HPV-16 variant were treated with chemoradiotherapy. After three months, it was observed that nine of the eleven patients (81.8%) achieved a complete response, five with the lineage A type, two with the lineage C type, and two with the lineage D type. The two cases of partial response and disease progression, one of each, occurred in lineage A. CONCLUSIONS: In addition to the small number of patients and HPV variants, we noticed a better response in patients with the HPV-16 lineage A. Increasing the sample size could be helpful to better assess the impact of HPV variants on cervical cancer treatment.

Effects of Euterpe oleracea Mart. extract on Candida spp. biofilms.

PROBLEM OF RESEARCH: Candida spp. biofilms are complex microbial communities that have been associated with increasing resistance to clinically available antifungal drugs. Hence, novel pharmacological approaches with ability to inhibit biofilm formation have been investigated. AIM OF STUDY: The aim was to analyze in vitro antifungal activity of Euterpe oleracea Mart. (açaí berry) extract on biofilm strains of Candida albicans, C. parapsilosis, and C. tropicalis that were formed on abiotic surfaces. REMARKABLE METHODOLOGY: Biofilms of C. albicans, C. parapsilosis, and C. tropicalis were grown in vitro. They were then treated with E. oleracea Mart. extract at different concentrations (7.8, 15.6, 31.2, 62.5, 125, 250, 500, and 1000 µg/mL) for evaluation of both biofilm removal and anti-biofilm activity. REMARKABLE RESULTS: All Candida species analyzed formed biofilms on abiotic surfaces. Yet, increased biofilm formation was displayed for C. tropicalis in comparison with the other two species. E. oleracea Mart. extract was shown to inhibit biofilm formation at all concentrations used when compared to no treatment (p < 0.05). SIGNIFICANCE OF THE STUDY: In the current study, the extract of E. oleracea Mart. demonstrated antifungal activity against Candida albicans, C. parapsilosis, and C. tropicalis biofilms, regardless of the dose utilized. These results are important to evaluate a natural product as antifungal for Candida species.

Ultrastructural changes induced by açaí (Euterpe oleracea Mart) in MCF-7 breast cancer cell line.

Açaí (Euterpe oleracea Mart) is an Amazon plant with many biological properties. Previous report of this group evidenced autophagy induction after treatment with açaí seed extract in MCF-7 breast cancer cell lines by acridine orange assay. The aim of this study was to evaluate the ultrastructural changes induced by açaí seed extract in MCF-7 breast cancer cell lines. First, MCF- 7 breast cancer cell line viability was evaluated by MTT assay. Acridine orange assay showed increase in the acidic compartments, suggesting autophagolysosome formation. These cells were treated with 25 µg/ml for 24 h and evaluated by transmission electron microscopy (MET). This analysis showed that açaí seed extract induced autophagy, confirmed by autophagolysosome formation. Furthermore, açaí seed extract increased the number of mitochondria, suggesting the enrollment of reactive oxygen species in autophagy.

PAGE-B and REACH-B Predicts the Risk of Developing Hepatocellular Carcinoma in Chronic Hepatitis B Patients from Northeast, Brazil.

This study aims to evaluate the accuracy of the PAGE-B and REACH-B scores in predicting the risk of developing HCC in patients with chronic hepatitis B regularly followed up at a reference service in the State of Maranhão. A historical, longitudinal, retrospective cohort study, carried out from the review of medical records of patients with chronic Hepatitis B. PAGE-B and REACH-B scores were calculated and the accuracy of the scores in predicting the risk of HCC in the studied population was evaluated. A total of 978 patients were included, with a median age of around 47 years, most of them female and not cirrhotic. HCC was identified in 34 patients. Thrombocytopenia, high viral load, male gender and age were associated with the occurrence of HCC. The ROC curve for the PAGE-B score showed a value of 0.78 and for the REACH-B score of 0.79. The cutoff point for PAGE-B was 11 points for greater sensitivity and for REACH-B 7.5 points considering greater sensitivity and 9.5 points considering greater specificity. PAGE-B and REACH-B scores were able to predict the risk of developing HCC in the studied population. The use of risk stratification scores is useful to reduce costs associated with HCC screening.

Evidence of Zika virus circulation in asymptomatic pregnant women in Northeast, Brazil.

BACKGROUND: Zika virus (ZIKV) is a flavivirus associated with microcephaly and other fetal anormalities. However, evidence of asymptomatic ZIKV infection in pregnant women is still scarce. This study investigated the prevalence of Zika infection in asymptomatic pregnant women attending two public maternities in Maranhão state, Northeast Brazil. METHODS: A total of 196 women were recruited at the time of delivery by convenience sampling from two maternity clinics in São Luís, Maranhão, Brazil, between April 2017 and June 2018. Venous blood, umbilical cord blood and placental fragments from maternal and fetal sides were collected from each subject. ZIKV infection was determined by reverse transcription polymerase chain reaction (RT-qPCR) for ZIKV and by serology (IgM and IgG). Nonspecific laboratory profiles (TORCH screen) were obtained from medical records. RESULTS: The participants were mostly from São Luís and were of 19-35 years of age. They had 10-15 years of schooling and they were of mixed race, married, and Catholic. ZIKV was identified in three umbilical cord samples and in nine placental fragments. Mothers with positive ZIKV RT-qPCR were in the age group older than 19 years. Of the 196 women tested by ZIKV rapid test, 6 and 117 women were positive for anti-ZIKV IgM and anti-ZIKV IgG antibodies, respectively. Placental Immunohistochemistry study detected ZIKV in all samples positive by RT-PCR. The newborns did not show any morphological and/or psychomotor abnormalities at birth. CONCLUSIONS: Asymptomatic ZIKV infection is frequent, but it was not associated to morphological and/or psychomotor abnormalities in the newborns up to 6 months post-birth. Although pathological abnormalities were not observed at birth, we cannot rule out the long term impact of apparent asymptomatic congenital ZIKV infection.

Pancytopenia as an initial manifestation of prostate cancer: a case report.

BACKGROUND: Prostate adenocarcinoma is the most frequent cancer type among men, followed by skin cancer. Patients with prostate cancer usually present lower urinary tract symptoms due to tumor involvement. Bone marrow invasion is associated with prostate cancer metastasis and is common if blastic lesions in bones are present but is very rare without a large bone involvement and uncommon as initial presentation. CASE PRESENTATION: We present a case of an 86-year-old Caucasian man with bone marrow invasion of prostate cancer without urological or bone-related symptoms and without prostate nodules. His findings were dyspnea, fatigue, and tachycardia. We detail the complete investigation of the case until we found the accurate diagnosis. The patient started treatment, but he had no response and so the oncology team started palliative care. CONCLUSION: Bone marrow invasion as an initial manifestation of prostate cancer is not common, especially if no prostatic lesions are found. This report is important to provide additional information about prostate cancer management.

Highly efficient antibiofilm and antifungal activity of green propolis against Candida species in dentistry materials.

This study evaluated the effect of green propolis extract on the adhesion and biofilm formation of Candida species in dentistry materials. Phytochemical analysis of green propolis extract was performed by high-performance liquid chromatography. Adhesion was quantified by counting the number of yeast cells adherent to dental material fragments in a Neubauer chamber. Biofilm formation was determined by counting colony-forming units recovered from dental material fragments. The intensity of biofilm adhesion was classified as negative, weak, moderate, strong, or very strong. Fifteen compounds, mainly flavonoids, were identified in green propolis extract. All strains adhered to and formed biofilms on the surfaces of the orthodontic materials studied. On steel and resin, yeast cell adhesion intensities were weak at all incubation times, except for those of Candida parapsilosis and C. tropicalis, which were moderate at 12 h. At 24 and 48 h, C. albicans formed biofilms on steel with moderate adhesion affinities; at 24 and 48 h, C. parapsilosis formed biofilms with very strong affinities. C. tropicalis formed biofilms with strong and very strong affinities at 24 and 48 h, respectively. On resin, all species displayed strong affinity for biofilm formation at 24 and 48 h, except for C. tropicalis, which displayed very strong affinity at only 48 h. Green propolis extract displayed antifungal activity and inhibited both adhesion and biofilm formation at 2.5 µg/mL. This study reinforces the idea that green propolis has antifungal activity and interferes with the virulence of Candida species.

Marine-Derived Penicillium purpurogenum Reduces Tumor Size and Ameliorates Inflammation in an Erlich Mice Model.

BACKGROUND: This study addresses the antitumoral properties of Penicillium purpurogenum isolated from a polluted lagoon in Northeastern Brazil. METHODS: Ethyl Acetate Extracellular Extract (EAE) was used. The metabolites were studied using direct infusion mass spectrometry. The solid Ehrlich tumor model was used for antitumor activity. Female Swiss mice were divided into groups (n = 10/group) as follows: The negative control (CTL-), treated with a phosphate buffered solution; the positive control (CTL+), treated with cyclophosphamide (25 mg/kg); extract treatments at doses of 4, 20, and 100 mg/kg; animals without tumors or treatments (Sham); and animals without tumors treated with an intermediate dose (EAE20). All treatments were performed intraperitoneally, daily, for 15 days. Subsequently, the animals were euthanized, and the tumor, lymphoid organs, and serum were used for immunological, histological, and biochemical parameter evaluations. RESULTS: The extract was rich in meroterpenoids. All doses significantly reduced tumor size, and the 20 and 100 mg/kg doses reduced tumor-associated inflammation and tumor necrosis. The extract also reduced the cellular infiltration of lymphoid organs and circulating TNF-α levels. The extract did not induce weight loss or renal and hepatic toxic changes. CONCLUSIONS: These results indicate that P. purpurogenum exhibits immunomodulatory and antitumor properties in vivo. Thus, fungal fermentation is a valid biotechnological approach to the production of antitumor agents.

Role of HPV 16 variants among cervical carcinoma samples from Northeastern Brazil.

BACKGROUND: Cervical cancer is the fourth most common type of cancer affecting women globally. In Brazil, it is the third most frequent type of cancer in women and HPV is present in approximately 90% of cases. Evidence suggests that variants of HPV 16 can interfere biologically and etiologically during the development of cervical cancer. METHODS: Cervix tumor fragments were collected, their DNA was extracted, and nested PCR was used to detect HPV. Positive samples were sequenced to determine the viral genotype. To characterize the HPV 16 strains, positive samples PCR was used to amplify the LCR and E6 regions of the HPV 16 virus. RESULTS: Data from 120 patients with cervical cancer were analyzed. Most women were between 41 and 54 years of age, had schooling until primary school, a family income between 1 and 2 times the minimum wage and were married/in a consensual union. There was no statistically significant association between HPV or socio-demographic variables and risk factors for cervical cancer (P <  0.05). HPV was present in 88 women (73%). The most prevalent types were HPV 16 (53.4%), HPV 18 (13.8%), HPV 35 (6.9%) and HPV 45 (5.7%). Of the 47 HPV 16 positive cases, variant A (49%) was present in 23 samples, followed by variant D in 20 cases (43%), and variants B and C in 2 cases each (4%). The most prevalent histological type of HPV 16 tumors was squamous cell carcinoma, followed by adenocarcinoma. There was a statistically significant association between HPV 16 variants and the tumors' histological types (P <  0.001). CONCLUSIONS: Knowledge of HPV 16 variants will provide data on their influence on the pathological and oncogenic aspects of cervical lesions.

Osteoporosis in primary care: an opportunity to approach risk factors.

INTRODUCTION: Climacteric women are susceptible to a number of changes, among them osteoporosis. Osteoporosis is a disease characterized by low bone mass and susceptibility to fracture. Currently, this disease is a public health issue, being necessary to recognize its risk factors. OBJECTIVES: Identify risk factors related to osteoporosis in women attending PROPIS/PROEX/UFMA, tracing a socio-demographic characterization and considering community lifestyles. MATERIAL AND METHODS: This is a transversal retrospective clinical with a quantitative approach study conducted between March and June 2013 in São Luís-MA with 107 women treated at the Programa de Práticas de Integralidade em Saúde (PROPIS - Integrality Health Practice Program). The study was approved by the University Hospital Ethics Committee of UFMA under opinion no. 362/07. Data were tabulated and analyzed in the epidemiological Epi-Info(®) software, version 3.4.1. RESULTS: The brown color was predominant, consensual relationships proved to be a protective factor and low education was a risk factor. The average age of the group with menopause was 54.1 years and without menopause was 31.3 years (p<0.0001). The average age of menopause was 43.7 years. The irregular menstrual cycle was a protective factor. The average number of pregnancies was 4.56 for the group with menopause and 2.45 for the group without menopause, with most births occurring normally (p<0.0001). Smoking, physical inactivity and caffeine intake were risk factors, while the absence of alcoholism and of soda intake were protective factors for the disease. CONCLUSION: The patients followed the socioeconomic and demographic profile of Maranhão. Most had menarche and menopause in appropriate periods, showed no positive family history of osteoporosis, did not usually drink alcohol, were sedentary and the caffeine intake was high.

Resistant tuberculosis in Maranhão, Brazil: a case series.

BACKGROUND: Mycobacterium tuberculosis multidrug resistance, especially against rifampicin and isoniazid, places pulmonary tuberculosis in the list of emerging diseases. The misuse of therapeutic regimens is one of its main predisposing factors. CASE PRESENTATION: Four clinical cases (three were brown and one black) with multidrug-resistant tuberculosis, treated in a reference hospital in the state of Maranhão, Brazil, were reported to evaluate the importance of radiological framework on disease evolution. CONCLUSION: The clinical framework showed a bad evolution and drug resistance, while radiology showed lung lesions, ranging from exudative infiltrates to lung parenchyma disintegration.

IgE serum concentration against airborne fungi in children with respiratory allergies.

BACKGROUND: To evaluate total and specific E immunoglobulin (IgE) antibody concentrations in underage subjects with respiratory allergic diseases. METHODS: This study was a transversal-type study in 100 underage subjects between 4 and 14 years old, with asthma and/or allergic rhinitis. Total and specific IgE were quantified for airborne fungi in the city of São Luís, Maranhão, Brazil. Five distinct regions-North, South, Center, East and West-were selected so fungi could be collected monthly for 1 year. Twenty genera were identified. Aspergillus, Penicillium, Fusarium and Neurospora were selected for the preparation of sensitizing antigens from ELISA dishes. IgE total concentrations were estimated using the same method. RESULTS: IgE total serum concentration was increased in 97 % of the atopic subjects: 75 % of the subjects presented increased IgE anti-Aspergillus concentrations, 87 % presented IgE anti-Penicillium, 45 % presented IgE anti-Fusarium, and 46 % presented IgE anti-Neurospora. CONCLUSIONS: Atopic subjects presented simultaneous IgE total and specific elevations for the tested fungi, possibly due to polysensitization caused by the presence of fungi in all of the areas all year. However, determining the clinical significance of the results was not yet possible because most of the data were isolated variables.

Family history in breast cancer in São Luís, Maranhão, Brazil.

BACKGROUND: Familial cancer includes some types of cancer aggregation without a well-defined inheritance pattern. Cancer genetics is an essential component of clinical practice in oncology. In Brazil, breast cancer is the leading cause of death in women. In Maranhão, studies on genetic predisposition are necessary to investigate the incidence and mortality rates. The aim of this study was to investigate familial cancer among relatives of women who died of breast cancer in São Luís, Brazil, constructing a pedigree to identify families with a hereditary predisposition, an important step in the early diagnosis of malignant tumors. METHODS: The city of São Luís is located on the Island of Maranhão, northeastern Brazil, with a population of 997,098 inhabitants mainly comprising blacks and mulattoes, including descendants of runaway slaves from the Amazon region itself. Data for pedigree construction were obtained from the records of 54 patients seen at the Aldenora Bello Institute of Oncology, São Luís, between 2000 and 2007, as well as by interview with relatives of the patients. RESULTS: The mean patient age at diagnosis was 39.5 years. Most women were mulattoes (36/54, 66.6%). A history of cancer was observed in 18 families, with 16 families possessing cases of cancer among first-degree relatives and five among second-degree relatives. CONCLUSION: A concentration of cancer cases was found in families of patients diagnosed until the age of 40, a finding demonstrating the importance of a family history prior to genetic counseling.

Gaucher disease in a family from Maranhão.

BACKGROUND: Gaucher disease is an inborn, autosomal recessive error of the metabolism which belongs to the group of lysosomal storage disorders. OBJECTIVE: This work reports on the treatment of Gaucher disease in several members of the same family from the countryside of Maranhão. METHODS: This was an observational, retrospective and prospective, descriptive case study about the efficacy of enzyme replacement therapy. RESULTS: The results showed that women were more affected (80% of patients) by the disease, age at diagnosis ranged from 24 to 33 years, the predominant ethnicity was mulatto (80%) and all cases were classified as type 1. The diagnosis of these patients was performed by measuring the levels of glucocerebrosidase and chitotriosidase enzymes and confirmed by genotyping. All patients suffering from Gaucher disease had low glucocerebrosidase levels. Before replacement therapy, hepatosplenomegaly was the most common clinical manifestation (100%) and osteopenia was seen in 80% of the cases. Regarding hematological manifestations, anemia and leukopenia were found in 40% of patients at diagnosis; however the hemoglobin and leukocyte levels were normalized after four years of therapy. Thrombocytopenia, observed in 20% of cases, was normalized after the second year of treatment. CONCLUSION: In these cases, despite gaps in the treatment as the family resides in the rural region of the state, the patients with Gaucher disease showed satisfactory therapeutic response over time.

Cerebral aspergillosis in a patient with leprosy and diabetes: a case report.

BACKGROUND: Opportunistic fungi are dispersed as airborne, ground and decaying matter. The second most frequent extra-pulmonary disease by Aspergillus is in the central nervous system. CASE PRESENTATION: The case subject was 55 years old, male, mulatto, and an assistant surveyor residing in Teresina, Piauí. He presented with headache, seizures, confusion, fever and left hemiparesis upon hospitalization in 2006 at Hospital São Marcos. Five years previously, he was diagnosed with diabetes mellitus, and 17 months previously he had acne margined by hyperpigmented areas and was diagnosed with leprosy. Laboratory tests indicated leukocytosis and magnetic resonance imaging showed an infarction in the right cerebral hemisphere. Cerebrospinal fluid examination showed 120 cells/mm(3) and was alcohol-resistant bacilli negative. Trans-sphenoidal surgery with biopsy showed inflammation was caused by infection with Aspergillus fumigatus. We initiated use of parenteral amphotericin B, but his condition worsened. He underwent another surgery to implant a reservoir of Ommaya-Hickmann, a subcutaneous catheter. We started liposomal amphotericin B 5 mg/kg in the reservoir on alternate days. He was discharged with a prescription of tegretol and fluconazole. CONCLUSION: This report has scientific interest because of the occurrence of angioinvasive cerebral aspergillosis in a diabetic patient, which is rarely reported. In conclusion, we suggest a definitive diagnosis of cerebral aspergillosis should not postpone quick effective treatment.

Seroprevalence of HTLV-1/2 among blood donors in the state of Maranhão, Brazil.

BACKGROUND: Infection with human T-lymphotropic virus 1 or 2 (HTLV-1/2) is a major health problem. There is a public health policy defining measures for state hematology and hemotherapy centers in Brazil, in order to avoid virus transmission through blood donors. OBJECTIVE: This study aimed to evaluate the seroprevalence of HTLV -1/2 in blood donors in the State of Maranhão, Brazil, during routine blood unit screening. METHODS: Screening tests of blood donors using the enzyme-linked immunosorbent assay (ELISA) to detect seropositivity for HTLV-1/2 performed at the Hematology and Hemotherapy Center of the State of Maranhão (HEMOMAR) between July of 2003 and December of 2009 were retrospectively evaluated. RESULTS: Of the 365,564 blood donors, 561 (0.15%) were HTLV-1/2-positive, of whom 72 (12.8%) performed the confirmatory test (Western blot). In donors who had a confirmatory test, 53 (73.6%) were positive. The ages of the infected individuals ranged from 18 to 65 years; 305 (54%) were aged over 40 years. Among the infected individuals, 309 (55%) were male, 399 (71%) were mixed-race, and 259 (46%) were single. Co-infections were frequently found, especially with hepatitis B (in 68.6% of the cases). CONCLUSION: The results obtained will contribute to the planning and implementation of control measures by the epidemiological surveillance agency of Maranhão, and will also contribute to reducing morbidity. The high seropositivity in a small sample in donors who had confirmatory tests indicates the need for confirmatory tests for all donors who initially test as seropositive.